Selective inhibition of monoamine oxidase type B by MDL 72145 increases the central effects of L-dopa without modifying its cardiovascular effects.
The potential of a new, potent, irreversible and selective inhibitor of monoamine oxidase type B, (E)-2-(3,4-dimethoxyphenyl)-3-fluorallyamine (MDL 72145), to augment the effects of L-DOPA in an animal model which reproduces the biochemical defect of Parkinson's disease has been evaluated. In rats bearing unilateral 6-hydroxydopamine lesions of the nigro-striatal dopamine pathways, both MDL 72145 and clorgyline, a selective inhibitor of MAO A, augmented the contralateral turning response to L-DOPA combined with carbidopa. The potential of inhibitors of MAO to interact adversely in the periphery with L-DOPA was investigated in the pithed rat; L-DOPA was given either intravenously or intraduodenally. Clorgyline consistently potentiated L-DOPA when given 18 h before testing. Neither MDL 72145 nor the selective inhibitor of MAO B, L-deprenyl, augmented the cardiovascular effects of intraduodenally administered L-DOPA. The data provide no reason to suppose that MDL 72145 would be very different in clinical use from L-deprenyl which is both effective and well-tolerated as an adjunct to the L-DOPA-based therapy of Parkinson's disease.
Fozard
J R
JR
Palfreyman
M G
MG
Robin
M
M
Zreika
M
M
D000499:Allylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects*; D006892:Hydroxydopamines / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000494:pharmacology
D000588:Amines; D006892:Hydroxydopamines; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D007980:Levodopa; D000499:Allylamine; C040051:2-(3,4-dimethoxyphenyl)-3-fluoroallylamine; D016627:Oxidopamine