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J Neural Transm. 2007 Apr 20;
Irer SV, Alper GE, Sezer ED, Duman E, Saatcioglu F, Yilmaz C.
Department of Biochemistry, Ege University Medical School, Izmir, Turkey.
The effect of l-deprenyl on tissue mRNA expressions of NOS isoforms and NO levels in an experimental diabetes mellitus model.
Diabetes and aging share some common mechanisms in their pathogenesis and diabetics are more prone to diseases of the elderly. Seeking for therapies likely to be proposed in the synchronised treatment of aging and diabetes is of great interest and l-deprenyl, a selective monoamine oxidase (MAO-B) inhibitor, is a possible candidate with its antioxidant, antiapoptotic and neuroprotective properties. Tissue MAO, NO and mRNA expression of nitric oxide (NO) synthase (NOS) isoforms were assessed in streptozotocin (STZ)-induced diabetic rats to evaluate the effect of l-deprenyl treatment. Twelve weeks of treatment had no significant effect on NO levels. Four-weeks treatment decreased tissue MAO activities and caused a decrease in expression of NOS-2 and NOS-3 in heart tissue of both controls and diabetics, and a decrease of liver NOS-3 expression in controls (p<0.05). l-Deprenyl, causing a decrease in tissue NOS expressions, might be of benefit by protecting the organism from the toxic radical effects of NO.
Ann Pharmacother. 2007 May;41(5):851-6.
Fohey KD, Hieber R, Nelson LA.
School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
The role of selegiline in the treatment of negative symptoms associated with schizophrenia.
OBJECTIVE: To evaluate the role of selegiline in the treatment of negative symptoms associated with schizophrenia. DATA SOURCES: MEDLINE (1966-January 2007) and PsychINFO (1967-January 2007) were searched, using the terms schizophrenia, negative symptoms, and selegiline. A bibliographic search was conducted, as well. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the search were evaluated. All primary literature was included in the review. DATA SYNTHESIS: Based on its dopamine-enhancing property, selegiline has been studied as augmentation to antipsychotic therapy for the treatment of negative symptoms associated with schizophrenia. The efficacy of low-dose oral selegiline for the treatment of negative symptoms has been evaluated in 1 case report, 2 open-label trials, and 2 controlled trials. The case report and both open-label trials report improvement of negative symptoms associated with low-dose oral selegiline. In 1 of the controlled trials, selegiline showed no difference in effect from that of placebo. These data are limited by small sample sizes. The largest controlled trial demonstrated a statistically significant difference between selegiline and placebo; however, the clinical significance is questionable, given that patients treated with selegiline were still experiencing marked negative symptoms at study completion. No comparative studies evaluating low-dose oral selegiline versus other augmentative treatment options for negative symptoms associated with schizophrenia exist at this time. CONCLUSIONS: Given the limitations of current literature, low-dose oral selegiline cannot be recommended for treatment of negative symptoms associated with schizophrenia. Additional controlled trials are needed to better delineate whether there is a role for selegiline in decreasing the burden of negative symptoms associated with schizophrenia.
Curr Med Res Opin. 2007 Apr;23(4):741-50.
Lew MF, Pahwa R, Leehey M, Bertoni J, Kricorian G.
The Zydis Selegiline Study Group. Keck/University of Southern California School of Medicine, Los Angeles, CA 90033, USA.
Safety and efficacy of newly formulated selegiline orally disintegrating tablets as an adjunct to levodopa in the management of 'off' episodes in patients with Parkinson's disease.
OBJECTIVE: Patients receiving levodopa for Parkinson's disease experience motor fluctuations and immobility ('off' episodes) between doses. This study assessed adjunctive Zelapar (selegiline orally disintegrating tablet (ODT)) for managing off episodes and for long-term safety. METHODS: This open-label extension evaluated long-term safety, efficacy, and tolerability of adjunctive selegiline ODT 2.5 mg in patients who completed either of two large phase 3 double-blind studies. The study was to end after 12 months but was amended to be open-ended. Investigators could increase levodopa doses and introduce controlled-release formulations of levodopa or dopamine agonists if warranted. Additionally, results of a small randomized trial of open-label selegiline ODT 1.25 mg in comparison to conventional selegiline was added only to the safety analysis. Efficacy variables included changes in daily off time and Patient's Global Impression of Improvement (PGI-I) and Clinical Global Impressions Severity of Disease (CGI-S) ratings. Safety assessments included adverse events and oropharyngeal findings. RESULTS: This study enrolled 254 patients: 248 from the large phase 3 studies (efficacy analysis) and an additional six from the prior open-label comparison (safety analysis) in order to evaluate a larger population for safety purposes. Mean reduction from baseline in daily off time was 9.4% (1.6 h) for patients previously given selegiline ODT, 6.0% (1.2 h) for those switched from placebo, and 8.1% (1.4 h) overall. PGI-I and CGI-S ratings indicated little or no change from baseline. Treatment-related adverse events occurred in 132 (52%) patients. No severe oral irritations were attributed to selegiline ODT or prompted discontinuation. CONCLUSIONS: Long-term selegiline ODT 2.5 mg/day was effective, safe, and well tolerated in patients with Parkinson's disease experiencing off episodes during levodopa therapy.
J Neural Transm Suppl. 2006;(71):143-56.
Magyar K, Palfi M, Jenei V, Szoko E.
Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
Deprenyl: from chemical synthesis to neuroprotection.
During the last decades (-)-deprenyl has become the golden standard of MAO-B inhibitors. It possesses dopamine potentiating and antioxidant properties; however, its effects cannot be explained solely by the enzyme inhibitory action. (-)-Deprenyl prevents the toxicity of certain selective neurotoxins and recently it was demonstrated to increase cell-cell adhesion as well. The complexity of its pharmacological effects reflects the action of both the parent compound and the active metabolites. (-)-Deprenyl and related propargylamines (DRPs) show neuroprotective features in a variety of in vitro and in vivo models that is dependent on the propargyl moiety. The main presumptive targets to date include glyceraldehyde-3-phosphate dehydrogenase, poly(ADP-ribose) polymerase, some kinase cascades, as well as pro- and antiapoptotic proteins, beside the inhibition of MAO-B. The antiapoptotic activity of DRPs converges upon the maintenance of mitochondrial integrity, due to the initiation of a complex transcriptional program, the details of which are yet to be elucidated.
J Clin Psychiatry. 2006 Sep;67(9):1354-1361.
Feiger AD, Rickels K, Rynn MA, Zimbroff DL, Robinson DS.
From the Department of Psychiatry, University of Colorado School of Medicine, Denver; Research
Selegiline Transdermal System for the Treatment of Major Depressive Disorder: An 8-Week,
OBJECTIVE: This study investigated the efficacy, safety, and tolerability of the selegiline
transdermal system (STS) administered in a dose range of 6 mg/24 hours to 12 mg/24 hours for
treating major depressive disorder (MDD). METHOD: Patients meeting DSM-IV criteria for MDD (N
= 265) were randomly assigned to blinded treatment with STS or a matching placebo patch for 8
weeks. Patients failing to meet or maintain protocol-defined therapeutic response criteria at
predetermined time points had their STS (or placebo) dose increased. Assessments were
conducted at weeks 1, 2, 3, 5, 6, and 8. Patients were not required to follow a
tyramine-restricted diet. The study ran from September 2001 through August 2002. RESULTS:
Selegiline transdermal system treatment resulted in significantly greater improvement (p
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Drug category:Antiparkinson agents
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