title: Chronic TVP-1012 (rasagiline) dose--activity response of monoamine oxidases A and B in the brain of the common marmoset.
abstract: The stereospecific form of the known acetylenic mechanism-based MAO-inhibitor AGN1135 (Rasagiline, TVP-1012) is devoid of sympathomimetic amphetamine-like properties. To evaluate the efficiency and selectivity of subcutaneous injections of TVP-1012 (dose range from 0.01 up to 10 mg/kg for 7 days) the activities of monoamine oxidases A and B (MAO-A,-B) were determined in different brain regions of the common marmoset. At a dose of 0.1 mg/kg TVP-1012, almost 80% of MAO-B activity is inhibited in all brain regions investigated (prefrontal and occipital cortex, cerebellum, caudate nucleus, putamen, nucleus accumbens). In contrast, MAO-A is not inhibited in putamen and nucleus accumbens. However, by increasing the TVP-1012 dose to 0.5 mg/kg, MAO-A is inhibited to a significant extent as well, concomitant to total inhibition of MAO-B. The results obtained indicate that TVP-1012 irreversibly inhibits both types of MAO in the common marmoset with selectivity for MAO-B at doses less than 0.5 mg/kg. TVP-1012 could be useful in studies requiring selective MAO-B inhibition without concomitant sympathomimetic amphetamine-like effects and could thus be of therapeutic interest for Parkinson's disease and retarded depression.
authors.affiliation: Department of Psychiatry, Julius-Maximilians-University, Würzburg, Federal Republic of Germany.
authors.forename: M E
authors.initials: ME
authors.lastname: Götz
authors.forename: W
authors.initials: W
authors.lastname: Breithaupt
authors.forename: J
authors.initials: J
authors.lastname: Sautter
authors.forename: A
authors.initials: A
authors.lastname: Kupsch
authors.forename: J
authors.initials: J
authors.lastname: Schwarz
authors.forename: W H
authors.initials: WH
authors.lastname: Oertel
authors.forename: M B
authors.initials: MB
authors.lastname: Youdim
authors.forename: P
authors.initials: P
authors.lastname: Riederer
authors.forename: M
authors.initials: M
authors.lastname: Gerlach
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D002144:Callithrix; D004305:Dose-Response Relationship, Drug; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D009928:Organ Specificity; D013997:Time Factors
chemical_list: D007189:Indans; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D008995:Monoamine Oxidase