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• Parkinson’s Disease
  • Amantadine/ Symmetrel
  • anticholinergics
  • Atamet
  • Cabaser or Cabaseril (cabergoline) (1)
  • Carbex or Eldepryl or SD-Deprenyl (selegiline hc)
  • Catechol-O-methyltransferase (COMT) inhibitors (1)
  • Comtan
  • Levodopa or Dopar or Larodopa (DA; dopamine receptor antagonist) (9)
  • Mirapex (pramipexole; ppdhc)
  • Parlodel (bromocriptine)
  • Permax (pergolide) (1)
  • propranolol (Inderal)
  • Rasagiline (selegiline) (3)
  • Requip (ropinirole or rophc)
  • Sifrol (pramipexole)
  • Sinemet & Sinemet CR (carbidopa-levodopa)
  • Symmetrel (antiviral as well ; amantadine)
  • Tasmar
  • Trivastal retard 50 OR Pronoran (piribedil) ,
  • Zelapar (& generic selegiline)
  • Zydis Apomorphine (apomorphine)
  • Hormone Replacement
  • Gene Therapy (1)
  • Needle Reflex Therapy
• Essential Tremor (7)
  • alprazolam/ Xanex
  • anti-convulsant
  • benzodiazepines
  • Beta-adrenergic blockers
  • clonazepam/ Klonopin
  • diazepam/ Valium
  • gabapentin (Neurontin)
  • lorazepam/ Ativan
  • primidone/ Mysoline (1)
  • propranolol/ Inderal (1)
  • zonisamide (zonegran) (1)
  • Hormone Replacement
  • Gene Therapy
  • Needle Reflex Therapy

(A small sampling of results from a January 15 to 28, 2007 MIB Abstract Alert search)

Go to Archive

Warning two parkinson's drugs pose heart valve risk

Research results from Stanford University, U.S., update neurology knowledge

Subthalamic Nucleus Stimulation in Parkinson's Disease Patients Intolerant to Levodopa.

Corrections: For the Record; 2

Parkinson Disease Therapy; Research from University of Connecticut, Department of Neurology yields new data on parkinson disease therapy

News from Neurologix highlights the latest developments

Prevalence of essential tremor in the territory of Lake Trasimeno, Italy: Results of a population-based study.

Warning two parkinson's drugs pose heart valve risk

Australian Doctor. Chatswood: Jan 19, 2007. pg. 4

Helen Carter

NEJM Doctors are encouraged to warn patients taking the anti-parkinsonian drugs pergolide and cabergoline about the risk of cardiac valve regurgitation, after two new studies confirmed the association.

The study of 11,000 UK patients found the ergot-derived dopamine agonists were the only drugs among six dopamine agonists investigated that were significantly associated with cardiac valve disease.

The incidence of valvular regurgitation was six times higher among patients exposed to either pergolide (Permax) or cabergoline (Cabaser) than in patients who weren't exposed to dopamine agonists, the researchers found. But this risk only increased once use reached six months, and especially if doses exceeded 3mg a day.

Mr Greg Lan, managing director of pergolide manufacturer Aspen Pharmacare, said the company would write to GPs and specialists reinforcing the association, and would revise product information to highlight valvulopathy risks.

The Therapeutic Goods Administration is also reviewing the studies to decide if existing PI warnings should be strengthened.

Pfizer confirmed it was reviewing the cardiac safety of cabergoline with the TGA.

The Italian study of echocardiograms in 155 patients with Parkinson's disease taking dopamine agonists and 90 controls found clinically important regurgitation in 28% of patients taking cabergoline, 23% taking pergolide, 0% taking non-ergot drugs and 5% of controls.

Professor Mal Horne, director of the movement disorders clinic at St Vincent's Hospital in Melbourne and a neurologist specialising in Parkinson's disease, said the findings emphasised the need for pre-treatment and regular follow-up echocardiograms.

He also suggested regular chest/abdomen CT because ergot drugs were associated with pulmonary fibrosis and fibrosis of retroperitoneal tissue, the same process in fibrosis of the mitral valve.

Professor Horne said therapy should stop if valvulopathy was found because doing so appeared to halt the process.

Australia's Adverse Drug Reaction Committee has received six reports of cardiac valve abnormalities associated with the medications.

The drugs are potent 5-HT2B agonists, as are the anorectic fenfluramine and anti-migraine drugs dihydroergotamine, methysergide and ergotamine.

Mr Rodney Whyte, pharmacist at the drug information centre at Monash Medical Centre in Melbourne, said doctors might need to re-evaluate prolonged use of these agents.

New England Journal of Medicine 2007; 356:29-46.

Proquest Identifier: 1206867551
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Research results from Stanford University, U.S., update neurology knowledge

Genetics & Environmental Health Week January 24, 2007

New neurology study findings recently were published by scientists from Stanford University, U.S.

Study 1: Current study results from the report, "COMT genotype, gender and cognition in community-dwelling, older adults," have been published. "A common polymorphism (Val158Met) in the gene encoding for the catechol-O-methyltransferase (COMT) enzyme has been associated with differences in prefrontal cognitive function in schizophrenic patients and healthy adults. While several studies indicate that the Met allele is associated with better performance on measures of executive function, working memory and verbal fluency, results have been inconsistent," scientists writing in the journal Neuroscience Letters report.

"Furthermore, fewer studies have investigated this relationship in older adults, a group known to experience impairments in prefrontal cognitive functions. Additionally, findings vary according to the gender distribution of study participants. We examined whether COMT genotype interacted with gender to impact cognition in a cohort of 163 healthy, older adults. Memory, verbal ability and areas of prefrontal cognitive function, including attention, speed-of-processing, and executive function, were assessed. We found no significant association between COMT genotype and any cognitive measure. However, gender interacted with COMT genotype to impact cognitive performance. Males homozygous for the Val allele performed better than both the Val/Met and Met/Met groups on measures of delayed recall. Heterozygous women performed better than their homozygous counterparts on the measure of verbal ability. These findings suggest that gender may be an important variable in consideration of the impact of COMT on cognition," wrote R. O'Hara and colleagues, Stanford University.

The researchers concluded: "Further, when gender is taken into consideration, any negative impact of COMT genotype may extend to cognitive domains other than those associated with prefrontal regions."

O'Hara and colleagues published their study in Neuroscience Letters (COMT genotype, gender and cognition in community-dwelling, older adults. Neuroscience Letters, 2006;409(3):205-9).

Additional information can be obtained by contacting R. O'Hara, Stanford University School of Medicine, Dept. of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305-5550 U.S.

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Subthalamic Nucleus Stimulation in Parkinson's Disease Patients Intolerant to Levodopa.

Stereotact Funct Neurosurg. 2007 Jan 26;85(4):169-174 [Epub ahead of print]

Lyons KE, Davis JT, Pahwa R.

University of Kansas Medical Center, Department of Neurology, Kansas City, Kans., USA.

Levodopa responsiveness has been shown to be the best predictor of improvement after subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD). The objective of this study was to assess the effect of STN DBS on PD patients intolerant to levodopa due to severe acute side effects such as intolerable nausea. There were 10 patients in the study who received STN DBS for PD. Five patients who were intolerant to levodopa were matched based on age, disease duration, sex and presurgical disease severity to 5 patients taking levodopa and demonstrating a good levodopa response. Both groups had a significant improvement in Unified Parkinson's Disease Rating Scale activities of daily living and motor subscales as well as tremor, rigidity and bradykinesia scores at 3, 6 and 12 months after surgery compared to baseline, and these improvements were equivalent between the two groups. Patient global ratings also indicated significant improvements at all follow-up visits. There were no differences in stimulator settings between the two groups at the 3-, 6- or 12-month follow-up visits. In conclusion, although levodopa responsiveness is the best predictor for outcome after STN DBS, carefully selected PD patients intolerant to levodopa can have significant improvement. Copyright (c) 2007 S. Karger AG, Basel.

PreMedline Identifier: 17259749

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Levodopa and the risk of melanoma.

Lancet. 2007 Jan 27;369(9558):257-8.

Zanetti R, Rosso S.

Piedmont Cancer Registry-CPO, Turin 10123, Italy. roberto.zanetti@cpo.it

<< No Abstract Available >>

PreMedline Identifier: 17258651

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The effect of Madopar on the pharmacokinetics of ropinirole in healthy Chinese volunteers.

J Pharm Biomed Anal. 2007 Jan 17;43(2):774-8. Epub 2006 Oct 19.

Wen AD, Jia YY, Luo XX, Bi LL, Chen XY, Zhong DF.

Department of Pharmacy, Xi'jing Hospital, Fourth Military Medical University, Xi'an 710032, PR China. adwen@fmmu.edu.cn

Ropinirole is a nonergoline dopamine D(2)-receptor agonist and has been proven to be effective in both monotherapy and combination therapy for idiopathic Parkinson's disease. The purpose of the present study was to examine the effect of Madopar on the pharmacokinetics of ropinirole in healthy Chinese volunteers by using liquid chromatography tandem mass spectrometry (HPLC/MS/MS). A single dose of 1mg ropinirole was given orally after administration of the placebo or Madopar (containing 200 mg levodopa and 50 mg benserazide) to six healthy males and six healthy females in a cross-over randomized study with a minimum washout period of 8 days. Pharmacokinetic parameters were calculated for both treatments. Coadministration of ropinirole and Madopar did not result in a notable change in rate or extent of availability of ropinirole, as shown by the ratios (90% confidence intervals) of 1.045 (0.900, 1.222) for C(max) (maximum plasma concentration) and 1.167 (1.086, 1.262) for AUC(0-inf) (the area under the concentration-time curve). Likewise, no significant difference in any of the other pharmacokinetic parameters [T(max) (the time needed to reach the C(max)), MRT (mean residence time), volume of distribution (V/F), and clearance (CL/F)] was observed between the treatment groups. No clinically relevant adverse effects were detected under either conditions and there are no pharmacokinetic grounds for adjusting the dose of ropinirole when given in combination with Madopar in Chinese patients.

PreMedline Identifier: 17055209

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Rat model of Parkinson's disease with bilateral motor abnormalities, reversible with levodopa, and dyskinesias.

Mov Disord. 2007 Jan 17; [Epub ahead of print]

Paille V, Henry V, Lescaudron L, Brachet P, Damier P.

INSERM, UMR 643 and Institut de Transplantation et de Recherche en Transplantation, CHU, Nantes, France.

Parkinson's disease (PD) is characterized by the bilateral degeneration of the midbrain dopamine-containing neurons with the most severe lesion in the posterolateral part of the substantia nigra pars compacta (SNpc). In humans, such lesions lead to specific motor abnormalities (i.e., akinesia, rigidity, and tremor) that are greatly improved by levodopa treatment. After a few years, the beneficial effect of the treatment is frequently offset by the development of dyskinesias. To improve treatment strategies, an animal model showing most of the histological and clinical characteristics of the human disease is mandatory. Ten rats received a bilateral injection of small doses of 6-OHDA in the medial forebrain bundle (MFB) and were compared with five sham-lesioned rats. The 6-OHDA-lesioned rats progressively developed abnormal motor behavior (assessed by the stepping test) compared with the sham-lesioned rats. The lesioned rats greatly improved under levodopa treatment, but developed concomitant dyskinesias. All 6-OHDA-lesioned animals had bilateral partial lesions of the SNpc, with the most severe lesion being in its posterolateral part. There was a significant correlation between the severity of the dopaminergic cell loss and the severity of the levodopa-induced dyskinesias. These rats constitute an interesting model of PD, sharing some of the main characteristics of the human disease. (c) 2006 Movement Disorder Society.

PreMedline Identifier: 17230470

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Pharmacy update - Parkinson's disease: a case study

Chemist & Druggist. London: Jan 27, 2007. pg. 17

Stalevo; ropinirole; Sinemet Plus; levodopa; dopamine; acetylcholine; carbidopa; benserazide; co-beneldopa (Madopar); co- careldopa; entacapone; bromocriptine; cabergoline; lisuride; pergolide; rotigotine; pramipexole; apomorphine; Selegiline; rasagiline; Amantadine

This case study describes a patient feeling unwell after a change in Parkinson's disease medication

Mary Allen

Joe McCarthy is 70 years old. You have been dispensing medicines for his Parkinson's disease for about five years. When he arrives in the pharmacy one morning you feel quite shocked at his deterioration since you last saw him some months ago. He seems anxious and "wants a word". He used to travel across town to a GP in whom he had great trust, but this doctor has recently retired, and for that reason and because of his reduced mobility, he has registered with the local GP practice. But he feels unsure about the new doctors.

His immediate problem is twofold: he is confused about a new drug the hospital prescribed and dispensed recently and he is very constipated.

You can see that he is anxious and suggest that he comes back this afternoon when it is less busy, arranging to do an MUR at the same time.

**Click Here to view the full text of this abstract**

Proquest Identifier: 1206479551
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Tardive Dyskinesia Therapy; New findings in tardive dyskinesia therapy described from University of Ioannina, Department of Neurology

Health & Medicine Week. Atlanta: Jan 15, 2007. pg. 470

Konitsiotis, S

2007 JAN 15 - (NewsRx.com) -- Scientists discuss in "Levetiracetam in tardive dyskinesia: an open label study" new findings in tardive dyskinesia. "Levetiracetam (LEV), a novel antiepileptic drug, has demonstrated antidyskinetic effect in preclinical animal models of Parkinson's disease (PD) and in one open label study in PD patients with levodopa-induced dyskinesia. The acute antidyskinetic effects of LEV in patients with tardive dyskinesia were evaluated in an open label study," scientists in Ioannina, Greece report.

"Eight patients received oral LEV (1,000 mg/day) for 1 month and blinded evaluations were performed at baseline and at the end of the treatment period. A significant reduction of the abnormal movements was recorded while psychiatric symptoms did not worsen and the adverse event profile was benign," wrote S. Konitsiotis and colleagues, University of Ioannina, Department of Neurology.

The researchers concluded: "LEV may be efficacious for the treatment of tardive dyskinesia and deserves further clinical testing."

Konitsiotis and colleagues published their study in Movement Disorders (Levetiracetam in tardive dyskinesia: an open label study. Movement Disorders, 2006;21(8):1219-21).

For additional information, contact S. Konitsiotis, University of Ioannina Medical School, Dept. of Neurology, Ioannina, Greece.

The publisher's contact information for the journal Movement Disorders is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Proquest Identifier: 1191587171
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Parkinson Disease Therapy; Scientists at University Hospital detail research in parkinson disease therapy

Pain & Central Nervous System Week. Atlanta: Jan 15, 2007. pg. 104

Funkiewiez, A

2007 JAN 15 - (NewsRx.com) -- Data detailed in "Effects of levodopa and subthalamic nucleus stimulation on cognitive and affective functioning in Parkinson's disease" have been presented. According to a study from Grenoble, France, "In Parkinson's disease (PD), levodopa and subthalamic nucleus (STN) stimulation lead to major improvement in motor symptoms. Effects of both treatments on cognition and affective status are less well understood."

"Motor, cognitive, and affective symptoms may relate to the dysfunctioning of parallel cortico-striatal loops. The aim of this study was to assess cognition, behavior, and mood, with and without both treatments in the same group of PD patients. A group of 22 nondemented PD patients was included in this study. Patients were tested twice before surgery (off and on levodopa) and twice 3 months after surgery (OFF and ON STN stimulation, off levodopa). Cognitive and affective effects of STN stimulation and levodopa had some common, but also different, effects. STN stimulation improved performance on the planning test, associated with the dorsolateral prefrontal cortex. However, the treatments had opposite effects on tests associated with the orbitofrontal cortex; specifically, levodopa impaired while STN stimulation improved performance on the extinction phase of a reversal/extinction task. Acutely, both treatments improved motivation and decreased fatigue and anxiety. On chronic treatment (3 months after surgery), depression improved, whereas apathy worsened 3 months after surgery," wrote A. Funkiewiez and colleagues, University Hospital.

The researchers concluded: "To conclude, there were significant but contrasting effects of levodopa and STN stimulation on cognition and affective functions."

Funkiewiez and colleagues published the results of their research in Movement Disorders (Effects of levodopa and subthalamic nucleus stimulation on cognitive and affective functioning in Parkinson's disease. Movement Disorders, 2006;21(10):1656-62).

For additional information, contact A. Funkiewiez, Joseph Fourier University of Grenoble, Dept. of Clinical and Biological Neurosciences, University Hospital of Grenoble and INSERM U318, Grenoble, France.

The publisher of the journal Movement Disorders can be contacted at: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Proquest Identifier: 1191581801
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Parkinson Disease; Research on parkinson disease described by scientists at Baylor College of Medicine, Department of Neurology

Pain & Central Nervous System Week. Atlanta: Jan 15, 2007. pg. 89

2007 JAN 15 - (NewsRx.com) -- A new study, "Subthalamic deep brain stimulation in patients with a previous pallidotomy," is now available. "The safety and efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients who have had a previous unilateral pallidotomy is not clear. We identified 10 patients (9 male) at the Baylor College of Medicine Parkinson's Disease Center who underwent STN DBS after prior unilateral pallidotomy," scientists writing in the journal Movement Disorders report.

"Demographics, efficacy as determined by off Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, and levodopa equivalent dosing were analyzed. We then compared these to an age- and sex-matched group of 25 DBS patients who had no prior pallidotomy. After their initial pallidotomy (mean age, 51.8 +-10.8 years), the mean UPDRS motor off medicine scores improved from 51.3 +-14.3 to 34.9 +-12.8, and the UPDRS dyskinesia score improved from 1.8 +-1.0 to 0.8 +-0.7. Their STN DBS off UPDRS motor scores (mean age, 56.0 +-10.2 years) improved by 16.0% from 53.1 +-9.7 (range, 42- 68) to 44.6 +-11.1 (range, 25-67). In contrast, the UPDRS off motor scores in a control group of 25 DBS patients improved by 49.9%, from 49.7 +-11.1 to 25.7 +-18.9, (16.0% vs. 49.9%; p<0.001). Changes in UPDRS dyskinesia scores were similar in both groups. AE thought to be related to the STN DBS following pallidotomy included worse dysarthria (three) and worse balance (two). STN DBS patients with prior pallidotomy had less improvement in UPDRS off motor score compared to other STN DBS patients, despite relatively good outcomes immediately after their pallidotomy," wrote W.G. Ondo and colleagues, Baylor College of Medicine, Department of Neurology.

The researchers concluded: "This may be partially due to a selection bias, but it may also indicate that prior pallidotomy is a negative predictor of outcome of STN DBS and should be considered in patient selection."

Ondo and colleagues published their study in Movement Disorders (Subthalamic deep brain stimulation in patients with a previous pallidotomy. Movement Disorders, 2006;21(8):1252-4).

Additional information can be obtained by contacting W.G. Ondo, Baylor College of Medicine, Dept. of Neurology, Houston, Texas U.S.

The publisher of the journal Movement Disorders can be contacted at: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Proquest Identifier: 1191581421
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In brief: The Neupro rotigotine patch

Chemist & Druggist January 27, 2007

The Neupro rotigotine patch is now available from Schwarz Pharma as an adjuvant to levodopa in late-stage Parkinson's disease. The treatment is said to offer a convenient means of reducing `off'-time, and improving early morning motor control, sleep quality and drowsiness.

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Corrections: For the Record; 2

New York Times. (Late Edition (East Coast)). New York, N.Y.: Jan 19, 2007. pg. A.2

An article on Jan 4, 2007 about heart-valve problems linked to two drugs for Parkinson's disease misstated the year that one of them, Permax, added a black-box warning label, the strongest warning required by the Food and Drug Administration. It was 2006, not 2003.

Proquest Identifier: 1201004481
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Parkinson Disease Therapy; Research from University of Connecticut, Department of Neurology yields new data on parkinson disease therapy

Pain & Central Nervous System Week. Atlanta: Jan 15, 2007. pg. 102

2007 JAN 15 - (NewsRx.com) -- New investigation results, "Effects of tyramine administration in Parkinson's disease patients treated with selective MAO-B inhibitor rasagiline," are detailed in a study published in Movement Disorders. According to recent research from the United States, "Rasagiline is a novel, potent, and selective MAO- B inhibitor shown to be effective for Parkinson's disease. Traditional nonselective MAO inhibitors have been associated with dietary tyramine interactions that can induce hypertensive reactions."

"To test safety, tyramine challenges (50-75 mg) were performed in 72 rasagiline-treated and 38 placebo-treated Parkinson's disease (PD) patients at the end of two double-blind placebo-controlled trials of rasagiline. An abnormal pressor response was prespecified as three consecutive measurements of systolic blood pressure (BP) increases of >or=30 mm Hg and/or bradycardia of <40 beats/min. In the first study involving 55 patients with early PD on rasagiline monotherapy, no patients randomized to rasagiline (1 mg/2 mg; n=38) or placebo (n=17) developed systolic BP (SBP) or heart rate changes indicative of a tyramine reaction. In the second trial involving 55 levodopa-treated patients, 3 of 22 subjects on rasagiline 0.5 mg/ day and 1 of 21 subjects on placebo developed asymptomatic, self- limiting SBP elevations >or=30 mm Hg on three measurements. No subject on 1 mg/day rasagiline (0/12) experienced significant BP or heart rate changes following tyramine ingestion," wrote J.A. deMarcaida and colleagues, University of Connecticut, Department of Neurology.

The researchers concluded: "These data demonstrate that rasagiline 0.5 to 2 mg daily is not associated with clinically significant tyramine reactions and can be used as monotherapy or adjunct to levodopa in PD patients without specific dietary tyramine restriction."

deMarcaida and colleagues published their study in Movement Disorders (Effects of tyramine administration in Parkinson's disease patients treated with selective MAO-B inhibitor rasagiline. Movement Disorders, 2006;21(10):1716-21).

For additional information, contact J.A. deMarcaida, University of Connecticut, Dept. of Neurology, Farmington, Connecticut U.S.

Publisher contact information for the journal Movement Disorders is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Proquest Identifier: 1191581741
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New neurobiology study findings have been reported from National Parkinson Foundation

Proteomics Weekly January 15, 2007

A new study, "Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism," is now available. "The anti-Parkinson monoamine oxidase (MAO)-B inhibitor rasagiline (Azilect) was shown to possess neuroprotective activities, involving the induction of brain-derived-and glial cell line-derived neurotrophic factors (BDNF, GDNF). Employing conventional neurochemical techniques, transcriptomics and proteomic screening tools combined with a biology-based clustering method, we show that rasagiline, given chronically post-MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), exerts neurorescue/neurotrophic activity in mice midbrain dopamine neurons," scientists in Haifa, Israel report.

"Rasagiline induced the activation of cell signaling mediators associated with neurotrophic factors responsive-tyrosine kinase receptor (Trk) pathway including ShcC, SOS, AF6, Rin1 and Ras and the increase in the Trk-downstream effector phosphatidylinositol 3 kinase (PI3K) protein. Confirmatory Western and immunohistochemical analyses indicated activation of the substrate of PI3K, Akt and phosphorylative inactivation of glycogen synthase kinase-3beta and Raf1. Thus, the activation of Ras-PI3K-Akt survival pathway may contribute to rasagiline-mediated neurorescue effect," wrote Y. Sagi and colleagues, National Parkinson Foundation.

The researchers concluded: "It is interesting to determine whether a similar effect is seen in parkinsonian patients after long-term treatment with rasagiline."

Sagi and colleagues published their study in Neurobiology of Disease (Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism. Neurobiology of Disease, 2007;25(1):35-44).

For additional information, contact Y. Sagi, Eve Topf and U.S. National Parkinson Foundation, Centers of Excellence for Neurodegenerative Diseases Research and Dept. of Pharmacology, Technion-Rappaport Faculty of Medicine, POB 9697, 31096 Haifa, Israel.

The publisher's contact information for the journal Neurobiology of Disease is: Academic Press Inc. Elsevier Science, 525 B St., Ste. 1900, San Diego, CA 92101-4495, USA.

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Disease modification trial for Parkinson disease completes enrollment

Pharma Business Week January 22, 2007

The largest clinical study to investigate disease modification in early Parkinson disease (PD) has completed enrollment.

The ADAGIO (attenuation of disease progression with Azilect given once daily) study is evaluating approximately 1200 recently diagnosed patients worldwide to determine if treatment with once-daily Azilect (rasagiline tablets) can slow the progression of PD.

"We are excited about the approval of Azilect in the U.S. as a once-daily treatment for PD as both initial monotherapy and as an adjunctive therapy to levodopa and by the completion of enrollment of this very important trial," said Larry Downey, president and chief executive officer of Teva Neuroscience, Inc.

To date, there are no PD therapies on the market shown to slow, halt, or reverse the progression of this neurodegenerative disease for the 1 million people in the United States suffering from Parkinson disease. PD continues to challenge researchers. Its symptoms can ultimately rob patients of everyday freedoms, like walking and maintaining control of movement. "The ADAGIO study is designed to separate the symptomatic improvement from any potential disease modifying activity," said Dr. Warren Olanow, professor and chairman of the department of neurology at Mount Sinai School of Medicine.

The double-blind, placebo-controlled phase of the study includes 2 active treatment groups receiving either 1 mg or 2 mg doses of AZILECT once daily, and 1 placebo-treated group for 36 weeks. After that period, study participants will either continue on their preassigned active treatment for another 36 weeks or, in the case of placebo patients, be switched to 1 of the 2 AZILECT treatment doses in a blinded fashion. Progression of PD will be assessed using the Total Score of the Unified Parkinson Disease Rating Scale during the last 36 weeks of the 72-week study.

The study is expected to be completed by mid-2008 and findings are expected to be made public later that year.

This article was prepared by Pharma Business Week editors from staff and other reports. Copyright 2007, Pharma Business Week via NewsRx.com.

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News from Neurologix highlights the latest developments

Lab Business Week January 21, 2007

News from Neurologix highlights the latest developments.

This trend article is an immediate alert from NewsRx to identify the most recent news developments at Neurologix.

Report 1: Having recently announced statistically significant clinical efficacy results of the first ever human gene therapy clinical trial for Parkinson disease at the Annual Meeting of the Society of Neuroscience in Atlanta, Neurologix (NRGX) is planning to move into the next stages of clinical development of its NLX gene therapy technology, including further studies for Parkinson disease and a Phase I human trial for temporal lobe epilepsy.

Neurologix, Inc. (NRGX) also announced its financial results for the quarter and nine months. For the quarter, the company reported a net loss of $2.5 million, as compared with $1.0 million for the quarter in 2005. The company reported a net loss applicable to common stock for the quarter of $2.8 million, or $0.10 per diluted share, as compared with $1.0 million, or $0.04 per share, for the same period in 2005.

The net loss applicable to common stock for the quarter ended September 30, 2006 includes charges of $277,000 related to preferred stock dividends in connection with the issuance of the company's Series C Preferred Stock. The company has cash, cash equivalents and short-term investments of approximately $11.7 million.

For the nine months, the company reported a net loss of $5.6 million, as compared with $3.5 million for the nine months in 2005. The company reported a net loss applicable to common stock for the nine months of $8.7 million, or $0.33 per diluted share, as compared with $3.5 million, or $0.14 per diluted share, for the same period in 2005.

The net loss applicable to common stock for the nine months, includes charges of $3.0 million, or $0.11 per diluted share, related to accretion of a beneficial conversion feature ($2.6 million) and preferred stock dividends ($0.4 million) in connection with the issuance of the company's Series C Preferred Stock in May 2006.

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Prevalence of essential tremor in the territory of Lake Trasimeno, Italy: Results of a population-based study.

Mov Disord. 2007 Jan 26; [Epub ahead of print]

Mancini ML, Stracci F, Tambasco N, Sarchielli P, Rossi A, Calabresi P.

Neurologic Clinic, Department of Medical and Surgical Specialties and Public Health, University of Perugia, Italy.

Because of the great variability in previous epidemiological data, and in light of the more accurate definition and diagnostic criteria recently formulated, we designed the present study to evaluate the prevalence of essential tremor (ET) in an Italian population. The study population included 13,604 individuals, who represented all patients of 11 family doctors working in the Territory of Lake Trasimeno in central Italy. Assessment of the sample and selection of the suspected cases were carried out by the same family doctors, previously trained to apply the inclusion and exclusion criteria for the definition of ET based on the Classification Criteria of the Movement Disorder Society (1998) and the Guidelines of the Ad Hoc Committee (2000). The total population was assessed over a period of 12 months. The age-adjusted prevalence of ET was 1.21% (95% confidence interval, 0.83-1.76). The probability of presenting with ET tended to increase with age and males showed a 50% greater risk for developing ET (male/female ratio = 1.5 for each age class). Our results are in line with the most recent epidemiological findings, which suggest a lower prevalence of ET than in older studies. These results can be attributed to the application of more stringent diagnostic criteria. (c) 2007 Movement Disorder Society.

PreMedline Identifier: 17260338

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Dystonia gravidarum: A new case with a long follow-up.

Mov Disord. 2007 Jan 26; [Epub ahead of print]

Fasano A, Elia AE, Guidubaldi A, Tonali PA, Bentivoglio AR.
Istituto di Neurologia, Universita Cattolica del Sacro Cuore, Rome, Italy.

We report a case of cervical dystonia occurring in a 33-year-old without personal history of movement disorder but with family history of essential tremor, primigravid, primiparous woman at 1 weeks' amenorrhea, resolved completely after delivery in the course of 3 months. Dystonia never recurred in the following 5 years. Several neurological disorders are known to occur or worsen during pregnancy. As far as we know, this is the second reported case of dystonia occurring during pregnancy, thus confirming that dystonia gravidarum represents a new entity and should be considered in women of reproductive age affected by dystonia, especially when presenting with rapid-onset cervical dystonia. (c) 2007 Movement Disorder Society.

PreMedline Identifier: 17260334

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Spontaneous low threshold spike bursting in awake humans is different in different lateral thalamic nuclei.

Exp Brain Res. 2007 Jan 26; [Epub ahead of print]

Ohara S, Taghva A, Kim JH, Lenz FA.

Department of Neurosurgery, Meyer Building 7-113, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD, 21287-7713, USA, flenz1@jhmi.edu.

Spontaneous action potential bursts associated with low threshold calcium spikes (LTS) occur in multiple human lateral thalamic nuclei, each with different physiologic characteristics. We now test the hypothesis that different patterns of spontaneous LTS bursting occur in these nuclei during awake surgery in patients with essential tremor and the arm at rest. This protocol was chosen to minimize the effect of the patient's disease upon thalamic activity which is a potential confound in a surgical study of this type. Neuronal activity was studied in the human thalamic nuclei receiving somatic sensory input (Vc, ventral caudal), input from the deep cerebellar nuclei (Vim, ventral intermediate), or input from the pallidum (Vo, ventral oral). In each nucleus the burst rates were significantly greater than zero. Burst rates were higher in Vc than in Vim, while firing rates were lower. These findings suggest that neurons in Vc are hyperpolarized and have more frequent inhibitory events. Pre-burst inter-spike intervals (ISIs) were significantly longer in Vc, but were significantly shorter when corrected for the average ISIs between bursts (burst rate/inverse of the primary event rate). These results suggest that inhibitory events in Vc are of lower magnitude relative to a hyperpolarized resting membrane potential. Studies in many species demonstrate that input from the pallidum to the thalamus is inhibitory, suggesting that input to Vo is predominantly inhibitory. However, neurons in Vo have neither slower firing rates nor more frequent LTS bursts. Previous studies have found that spontaneous LTS is similar between classes of neurons within Vc, as defined by their response to thermal and painful stimuli. The differences in spontaneous LTS between human nuclei but not between functional classes within a nucleus may be a basic organizing principle of thalamic inhibitory circuitry.

PreMedline Identifier: 17256161

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Elderly-onset essential tremor is associated with dementia.

Publication Types Available: Comments, Letters

Neurology. 2007 Jan 16;68(3):242; author reply 243.

Munhoz RP, Teive HG.

<< No Abstract Available >>

PreMedline Identifier: 17224586

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Maxfield reveals benign tremors ; Secretary of state one of 10 million Americans with movement disorder

Wyoming Tribune - Eagle. Cheyenne, Wyo.: Jan 24, 2007. pg. A.3

Kevin Wingert

rep3@wyomingnews.com

CHEYENNE - Secretary of State Max Maxfield wants to quell any rumors from observers who've seen his trembling hands: He does not have Parkinson's disease or Multiple Sclerosis.

"Over the past several months, I have experienced tremors in my hands," Maxfield told an audience of media and government officials gathered Tuesday in the Capitol rotunda.

Those tremors led Maxfield to seek a diagnosis from Dr. Reed Schafer of Cheyenne Medical Specialists. Schafer, a neurologist for more than 20 years, diagnosed Maxfield with benign essential tremor disorder. It is a neurological condition that is marked by exaggerated shaking when an affected individual attempts purposeful movements, often with hands.

Roughly 10 million Americans have essential tremors, according to the Parkinson's Institute.

See ILLNESS, page A5

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Essential tremor doesn't stop determined leader

Redlands Daily Facts. Redlands, Calif.: Jan 23, 2007. pg. n/a

BOBBE MONK

REDLANDS - Stella Hollebeek has essential tremor, but she hasn't let that stop her.

Widow of a minister for the Christian Reformed Churches, she started a support group two years ago for those who share her problem. Now, she's seeking to expand its outreach.

Essential tremor is a neurologic disorder causing the hands, head, legs, body or voice to shake. While usually striking older people, it can begin at any age - even birth.

It is sometimes mistaken for Parkinson's disease, but it differs in that it is an "action" tremor, the shaking noticible when the person attempts to write, hold a cup, sew or talk.

Parkinson's is a more "passive" disease with the tremors occuring usually, but not always, while the person is quiet.

Medications help essential tremor, but like the disease itself, they differ from person to person. And, when medications fail to work, there is the possibility of surgery which might help control the shaking.

Hollebeek, who lives in the Redlands Christian Home, said some 10 million people in the United States alone suffer from essential tremor.

"It's a challenge to live wth," she said. She has had it for the past 10 years.

The disease began when her right hand began to shake, then her left began, too. Eventually it affected her voice.

Calling it a "doing tremor," because it's noticeable when she begins to do something, she found she cannot write longhand, but is able to print. And, she's tried various medications, some of which have helped.

She wants others who have essential tremor to join with her group, which meets at 10 a.m. the last Thursday of each month at the River Church, 459 E. Highland Ave., Redlands. The next meeting will be Jan. 25. Meeting times are listed in the Redlands Daily Facts "What's happening" calendar.

"We want to let them know about the support group," Hollebeek said.

She feels that many don't know the latest information on essential tremor and its treatments. Also, the support and understanding of others with the problem is comforting.

"We enjoy meeting together," she says of the six members that now make up the group.

"We share what helps and what doesn't help. We understand each other." Those who attend can share their concerns, or simply listen.

"We're very comfortable with each other."

There is no cost to join, Hollebeek said.

For information on the group, call Hollebeek at (909) 794-2609.

International Essential Tremor Foundation

What: Nonprofit, worldwide information, services and support organization promoting and funding research for people diagnosed with essential tremor.

Web site: www.essenialtremor.org

For more information: Write IETF at P.O. Box 14005, Lenexa, KS 66285-4005.

Bobbe Monk, formerly the Our Town editor for the Redlands Daily Facts, is a freelance writer who lives in Yucaipa.

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Artificial Neural Networks; Research results from Hospital, Department of Medical Physics update understanding of artificial neural networks

Medical Devices & Surgical Technology Week. Atlanta: Jan 21, 2007. pg. 24

Hamilton, D

2007 JAN 21 - (NewsRx.com) -- Scientists discuss in "Discrimination between parkinsonian syndrome and essential tremor using artificial neural network classification of quantified DaTSCAN data" new findings in artificial neural networks. According to recent research published in the journal Nuclear Medicine Communications, "In the semi-quantitative assessment of DaTSCAN images, it has been suggested that the ratio of tracer accumulation in the putamen to that in the caudate nucleus may be helpful and could allow parkinsonian syndromes progression to be assessed. Separation of ratio values has been reported when early Parkinson's disease is compared with essential tremor."

"The separation is lost, however, when the Parkinson's disease is not early stage. To evaluate whether a two-stage analysis can differentiate between parkinsonian syndromes, of various stages, and essential tremor, and whether such a two-stage analysis can be undertaken in a single step using artificial neural networks (ANNs). Data from 18 patients were analysed. Quantification was undertaken by manually drawing irregular regions of interest (ROIs): over each caudate nucleus and putamen and over an occipital cortex area near the posterior edge of the brain. A two-stage analysis was undertaken and was repeated, in a single step, using an ANN. The first stage, of the two-stage analysis, identified 12 patients with non-early parkinsonian syndromes. The remaining six patients were then successfully classified into early parkinsonian syndromes and essential tremor. The ANN analysis successfully discriminated parkinsonian syndromes from essential tremor, in all patients, in a single step. The two-stage process provides a method for classifying early disease without being compromised by the noise from non-early disease," wrote D. Hamilton and colleagues, Hospital, Department of Medical Physics.

The researchers concluded: "The results of the single stage ANN analysis were very definite and it may be considered to have potential in the quantification of DaTSCAN images for clinical use."

Hamilton and colleagues published their study in Nuclear Medicine Communications (Discrimination between parkinsonian syndrome and essential tremor using artificial neural network classification of quantified DaTSCAN data. Nuclear Medicine Communications, 2006;27(12):939-44).

For additional information, contact D. Hamilton, County Hospital, Dept. of Medical Physics, Lincoln, UK.

The publisher's contact information for the journal Nuclear Medicine Communications is: Lippincott Williams & Wilkins, 530 Walnut St., Philadelphia, PA 19106-3621, USA.

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Hand tremor may be genetic; medicines can control shakes; [Final Edition]

Beaumont Enterprise. Beaumont, Tex.: Jan 22, 2007. pg. B.2

Dr. Paul G. Donohue

Dear Dr. Donohue,

I have a tremor in my right arm and hand. I can hardly put on makeup. If I try to sip something, my hand shakes, and I end up spilling it. What can be done for this?

-- K.R.

Your tremor has the characteristics of essential tremor. As much as 5 percent of the population has it. It is usually an inherited problem that has to do with movement-control centers in your brain. Can you remember if your mother, father, uncles, aunts, brothers or sisters had it? It goes by another name -- familial tremor.

This tremor most often affects both hands and arms, but the dominant arm, because it's used so much, is the one that bothers people more. As you say, it makes getting a cup of tea to the lips a Herculean task. Fine work like sewing or fitting a screwdriver into a screw's groove becomes almost impossible. It can affect the head, the legs and the tongue. The voice might take on a trembling quality.

Alcohol can abolish the shaking, but it can't be used as treatment, for obvious reasons. Propranolol (Inderal) and primidone are two medicines that usually can quiet it.

If the tremor is so violent that it throws life into disorder or if medicines fail to control it, then procedures that stimulate certain brain structures are treatment options. Medicines should be able to control your tremor.

You and the many others who suffer from this common condition will greatly benefit by contacting the International Essential Tremor Foundation at (888) 387-3667 or at its Web site, www.essentialtremor.org.

Dr. Donohue

P.O. Box 536475

Orlando, FL 32853-6475 be07 0056 070123 N S 0000000000 00002106

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Hand tremor may be genetic; medicines can control shakes; [Final Edition]

Beaumont Enterprise. Beaumont, Tex.: Jan 22, 2007. pg. B.2

Dr. Paul G. Donohue

<< Click Here to view the abstract in primidone/ Mysoline & ET above >>

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A double-blind placebo-controlled trial of zonisamide (zonegran) in the treatment of essential tremor.

Mov Disord. 2007 Jan 15;22(2):279-82.

Zesiewicz TA, Ward CL, Hauser RA, Sanchez-Ramos J, Staffetti JF, Sullivan KL.

Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa, Florida 33612, USA. tzesiewi@hsc.usf.edu

Medical therapy for essential tremor (ET), a common movement disorder, is often inadequate. We performed a double-blind placebo-controlled randomized trial to evaluate the efficacy and tolerability of zonisamide (ZNS), an antiepileptic agent, in treating ET. Twenty patients (mean age, 60 +/- 15 years) with ET were randomized to receive ZNS or placebo. ZNS was initiated at a dosage of 100 mg/day and escalated to 200 mg/day at day 14. Patients were evaluated by accelerometry and the Fahn-Tolosa-Marin (FTM) rating scale at baseline and days 14 and 28, as well as the Clinical Global Impression (CGI-C) scale at day 28. At endpoint, subjects assigned to ZNS were taking a mean dosage of 160 +/- 50 mg/day. There were no significant improvements in the FTM total score or its subsections. Tremor amplitude as assessed by accelerometry significantly improved in the ZNS group compared to the placebo group at endpoint relative to baseline (-0.50 +/- 0.72 vs. 0.30 +/- 0.79 m/s(2); P = 0.03). On the CGI-C, 60% (n = 6) of patients in the ZNS group felt that their tremor was unchanged, while the remaining patients felt that their tremor was "minimally improved." Thirty percent (n = 3) of patients taking ZNS discontinued the study due to side effects (fatigue, headache, paresthesias) while taking 100 mg per day. ZNS did not provide significant improvements in clinical rating scales at study endpoint compared to placebo and was only modestly well tolerated. ZNS was effective in reducing tremor amplitude as measured by accelerometry. (c) 2006 Movement Disorder Society.

PreMedline Identifier: 17149715

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Pharmacy update - Parkinson's disease: a case study

Chemist & Druggist. London: Jan 27, 2007. pg. 17

**Click Here to return to abridged abstract**

Stalevo; ropinirole; Sinemet Plus; levodopa; dopamine; acetylcholine; carbidopa; benserazide; co-beneldopa (Madopar); co- careldopa; entacapone; bromocriptine; cabergoline; lisuride; pergolide; rotigotine; pramipexole; apomorphine; Selegiline; rasagiline; Amantadine

This case study describes a patient feeling unwell after a change in Parkinson's disease medication

Mary Allen

Joe McCarthy is 70 years old. You have been dispensing medicines for his Parkinson's disease for about five years. When he arrives in the pharmacy one morning you feel quite shocked at his deterioration since you last saw him some months ago. He seems anxious and "wants a word". He used to travel across town to a GP in whom he had great trust, but this doctor has recently retired, and for that reason and because of his reduced mobility, he has registered with the local GP practice. But he feels unsure about the new doctors.

His immediate problem is twofold: he is confused about a new drug the hospital prescribed and dispensed recently and he is very constipated.

You can see that he is anxious and suggest that he comes back this afternoon when it is less busy, arranging to do an MUR at the same time.

Later...

You ask about the drug confusion. At a recent hospital clinic appointment the neurologist had decided to switch Joe on to the combination drug, Stalevo, but Joe was confused as to which existing medicine it should replace . He felt pretty sure he should take it instead of his ropinirole. Most of his consultation time with the neurologist had focused on his occasional but increasing swallowing problems (for which he was now due to see a speech therapist), and he couldn't be sure he had remembered the drug change information correctly.

He had dropped his ropinirole and was continuing the Sinemet Plus "because he thought that was what the specialist had said", but he wasn't feeling well. He also "hated" the Stalevo as he felt the start of his constipation had coincided with the introduction of this medicine. And - while he was at it - he also wanted to mention his cough, which bothered him sometimes, particularly after eating.

You notice that his dyskinesias (jerky movements) seemed worse than when you last saw him.

Some questions

* Do you think Joe is taking his medicines correctly since seeing the hospital doctor?

* What could be the cause(s) of his recent constipation?

* What is the difference between Sinemet Plus and Sinemet, and why do both forms exist?

* For what are modified-release forms of levodopa useful?

* For what are dispersible forms of levodopa useful?

Drug management of PD

At present there is no cure for PD. Drugs are the mainstay of treatment, but physiotherapy, speech/language therapy, and occupational therapy also play an important role. Self-help strategies can be useful, particularly in early-onset PD. Surgery may help some PD patients.

The cause of PD is not fully understood but it is associated with degeneration of dopaminergic neurones in the substantia nigra in the mid-brain. Neuromuscular transmission associated with co-ordinated movement depends on a balance between the neurotransmitters dopamine and acetylcholine. Loss of dopamine upsets this balance, with PD symptoms occurring when about 70 to 80 per cent of the dopaminergic neurones are lost. PD patients may also have lower levels of other neurotransmitters, including serotonin.

Most PD drugs aim to restore the balance between the transmitters acetylcholine and dopamine in various ways by:

* Increasing levels of dopamine in the brain.

* Acting as dopamine receptor agonists.

* Blocking the activity of acetylcholine.

Joe's drugs are intended to do the first two of the above.

Increasing dopamine

Levodopa (in Sinemet and Stalevo) is a precursor of dopamine. When introduced about 40 years ago it produced dramatic benefits, but problems have arisen with longer-term use.

It has a short plasma half-life, but its effects can be prolonged by the use of adjunct drugs:

co-administered dopa decarboxylase inhibitors (DDCIs) such as carbidopa or benserazide inhibit the metabolism of levodopa to dopamine by the peripheral enzyme dopa decarboxylase before it reaches the brain where it is needed. A range of products containing co-beneldopa (Madopar) and co-careldopa (Sinemet), including normal- release oral dosage forms, modified-release forms and (for co- beneldopa) dispersible tablets, allows individual needs to be met at different times of day.

Dispersible forms are useful in the morning to 'kick-start' patients, or for patients with swallowing difficulties. Modified- release forms may reduce fluctuations in blood levels and are useful in patients who have been taking levodopa for some time to counteract the 'wearing-off' effect (see 'Longer-term problems' section).

Patients taking medicines using carbidopa as the DDCI need 70 to 100mg of carbidopa daily for full inhibition of peripheral dopa- decarboxylase to avoid side effects such as nausea and vomiting. Sinemet tablets are thus available with different ratios of levodopa and carbidopa, allowing tailored levodopa doses for individual need and ensuring a total daily dose of at least 70mg of carbidopa.

COMT inhibitors Further loss of levodopa occurs from metabolism by another enzyme, catechol O-methyl-transferase (COMT). The drug entacapone inhibits COMT, increasing the levels of levodopa and prolonging its half-life. It is available as 200mg tablets, licensed for use with co-beneldopa or co-careldopa for patients who experience 'end-of-dose' deterioration.

Administering entacapone with levodopa plus DDCI (as co- careldopa or co-beneldopa) can result in:

* An increase in effect of one to one and a half hours each day.

* A potential reduction in the dose of levodopa of around 100mg each day.

Stalevo, launched in 2003, combines levodopa, carbidopa and entacapone, and is indicated for the treatment of patients with end- of-dose motor fluctuations (see below) not stabilised on levodopa/ dopa decarboxylase (DDC) inhibitor treatment.

Some problems with levodopa

* Some patients cannot tolerate levodopa because of severe sickness, although domperidone is useful in controlling nausea and vomiting.

* Dyskinesias: too high a dose of levodopa (or use over a long period) may result in abnormal, involuntary movements including jerking, writhing, twitching and spasms.

* Confusion, hallucinations, mood swings or psychological changes may occur.

* Dietary protein can interfere with absorption of levodopa. Some doctors recommend eating less protein in the daytime and more in the evening, but any dietary changes should be discussed with doctors and dieticians.

* Levodopa may activate malignant melanoma, so should be avoided in people with a history of, or suffering from, a malignant melanoma.

Longer-term problems

Over time, levodopa therapy is associated with:

* 'Wearing off' of therapeutic effects, which occurs increasingly before the next dose is due or has begun to work.

* Increase in dyskinesias.

* 'On/off' effects becoming more frequent: patients suffer sudden switches from being 'on' (able to move and function) to being 'off' (immobile or 'freezing').

Fine-tuning the dose or frequency of levodopa products, or switching to other drugs may help. Eventually, it may be necessary to find an acceptable balance between symptom control and dyskinesias.

Dopamine receptor agonists

Dopamine agonists include bromocriptine, cabergoline, lisuride, pergolide, ropinirole, rotigotine, pramipexole and apomorphine. With the exception of apomorphine, used only in advanced disease, they are frequently used:

* In new patients instead of levodopa.

* With levodopa in more advanced disease.

Dopamine agonists usually have fewer long-term side effects, so are used for younger patients, delaying the need for levodopa. However, they do not improve overall motor performance as well as levodopa, and they are associated with more neuropsychiatric side effects.

More details of side effects associated with dopamine antagonists can be found in the British National Formulary and in the different summaries of product characteristics via the online electronic medicines compendium.

Other drugs used include:

* Anticholinergic drugs to reduce the effects of the central cholinergic excess occurring as a result of dopamine deficiency. They are generally less effective than the newer dopamine agonists. Drugs include benzatropine, biperiden, orphenadrine, procyclidine, and trihexyphenidyl .

* Monoamine-oxidase-B inhibitors Selegiline and rasagiline may be used with levodopa to reduce 'end-of-dose' deterioration in advanced PD by slowing down the metabolism of dopamine in the brain, resulting in a reduced dose need for levodopa of around 30 per cent. Early treatment with monotherapy sometimes delays the need for levodopa therapy. Note: serious interactions may occur with some anti-depressants, including fluoxetine and some other SSRIs, and some tricyclics.

* Amantadine improves mild bradykinesia, tremor and rigidity, although its effects may be modest. It is sometimes useful for dyskinesias in more advanced disease. Tolerance may develop and confusion and hallucinations occasionally occur. Its mode of action has been poorly understood, but it is now thought to act as an NMDA- receptor antagonist. NMDA-receptors are associated with the neurotransmitter glutamate. It is likely that a variety of neurological diseases are in part mediated by a final common pathway of neuronal injury involving excessive stimulation of glutamate receptors.

Back to Joe...

* Joe has misunderstood the neurologist's intention - the newly- prescribed Stalevo is to replace Sinemet-Plus, not the dopamine agonist ropinirole. This is confirmed when Joe brings you a copy of the consultant's letter to his GP, which states this clearly. Although Joe is an intelligent man, his anxieties about his worsening disease have perhaps made him forget this letter as a resource.

* He has been taking both Sinemet Plus and Stalevo for a few weeks now, and this might explain the increase in his dyskinesias, which can occur with high doses of levodopa.

* Because he is now receiving entacapone, a COMT inhibitor, he may even need less levodopa - dose reductions of between 10 and 30 per cent are often appropriate.

* His constipation may be caused by the newly-introduced entacapone or could be a result of his ongoing disease. You should discuss the routine use of a laxative such as lactulose with his GP, and suggest use of this laxative to Joe in the interim.

* Joe's constipation may be exacerbated by low fluid intake. He has already acknowledged his problems with swallowing, and he may avoid fluids because of this. In addition, it is likely that he keeps his fluid intake low because of mobility problems in getting to the toilet in time when he needs to empty his bladder. His disease may also make it difficult to undo his trousers - fiddly movements are often challenging for PD sufferers. Joe should be encouraged to discuss these difficulties with his doctors and - better - with a local PD specialist nurse if there is one. It is important that he remains well hydrated.

* Joe's ongoing cough may be caused by his reported swallowing difficulties resulting in some aspiration of food (which could explain the occurrence after eating). He should talk to the speech therapist and his GP about this.

* Joe needs reassurance about seeing his new GP. His disease will get worse over time and he needs to develop a good relationship with this doctor.

Mary Allen, FRPharmS, is a part-time community pharmacist in Hertfordshire.

The Parkinson's Disease Society of the UK is a useful source of information for patients, carers and professionals. Tel: 020 7931 8080.

This article can be downloaded from C+D's website at www.dotpharmacy.com along with the following articles:

1. Allen, M. Pharmacy Update: Parkinson's disease. 2004; 265 (April 10): 19-22.

http://www.dotpharmacy.co.uk/up1300.pdf

2. Allen, M. Pharmacy Update: Parkinson's disease: use of drugs in PD. 2004; 265 (April 17):25-8. www.dotpharmacy.co.uk/up1301.pdf

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