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

Neuropharmacology. 2002 Dec;43(7):1110-8. doi: 10.1016/s0028-3908(02)00216-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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