Pharmacological properties of the anti-Parkinson drug rasagiline; modification of endogenous brain amines, reserpine reversal, serotonergic and dopaminergic behaviours.

Abstract

Rasagiline [N-propargyl-1R(+)-aminoindan; TVP1012] is a potent irreversible monoamine oxidase (MAO) inhibitor with selectivity for type B of the enzyme, which is being developed for treatment of Parkinson's disease. In this study we examined effects of rasagiline on CNS monoamine levels, modification of behavioural response to L-tryptophan, fluoxetine and L-DOPA, and reversal of reserpine syndrome. Reserpine-induced ptosis was reversed by rasagiline at doses above 2 mg x kg(-1) i.p., which inhibit MAO-A as well as MAO-B, but not at MAO-B-selective doses. However, combination of rasagiline (10 mg x kg(-1) i.p.) with L-DOPA or L-tryptophan (50 mg x kg(-1) i.p.), or rasagiline (10 mg x kg(-1) p.o.) with fluoxetine (10 mg x kg(-1) p.o.), did not induce the behavioural hyperactivity syndrome which is seen following inhibition of both MAO-A and MAO-B by tranylcypromine together with the monoamine precursors. Following oral administration, levels of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and dopamine (DA) were unaffected in hippocampus and striatum after single doses of rasagiline up to 2 mg x kg(-1). Following chronic oral administration (21 days, one dose daily), levels of NA, 5-HT and DA in hippocampus and striatum were unaffected by rasagiline at doses up to 1 mg x kg(-1). Rasagiline does not modify CNS monoamine tissue levels or monoamine-induced behavioural syndromes at doses which selectively inhibit MAO-B but not MAO-A.

• Authors: John P M Finberg, Moussa B H Youdim
• Journal: Neuropharmacology (Neuropharmacology) Vol. 43 Issue 7 Pg. 1110-8 (Dec 2002) ISSN: 0028-3908 [Print] England
• PMID: 12504917 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiparkinson Agents
• Biogenic Amines
• Indans
• rasagiline
• Serotonin
• Reserpine
• Dopamine

Topics

• Animals
• Antiparkinson Agents (pharmacology)
• Biogenic Amines (metabolism)
• Blepharoptosis (chemically induced, metabolism)
• Brain (drug effects, metabolism)
• Dopamine (metabolism)
• Dose-Response Relationship, Drug
• Indans (pharmacology)
• Male
• Motor Activity (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Reserpine (toxicity)
• Serotonin (metabolism)