Effect of a selective MAO-A inhibitor (Ro 41-1049) on striatal L-dopa and dopamine metabolism: an in vivo study.
We administered Ro 41-1049, an inhibitor of the enzyme monoamine oxidase type A (MAO-A) to rats and monitored extracellular catecholamine levels in the corpus striatum before and after the intraperitoneal (IP) administration of a bolus of L-dopa. Acute administration of Ro 41-1049 (1-50 mg/kg IP) produced a dose-dependent decrease in basal levels of the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and an increase in basal levels of dopamine. In rats treated with Ro 41-1049 (20 mg/kg IP), L-dopa administration (100 mg/kg IP) produced a greater increase in striatal levels of dopamine than it did in controls, while DOPAC and HVA formation was attenuated. We conclude that inhibition of central MAO-A activity promotes synaptic accumulation of dopamine following administration of pharmacological doses of L-dopa.
Brannan
T
T
Department of Neurology, Mount Sinai School of Medicine, New York, NY.
Prikhojan
A
A
Yahr
M D
MD
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002396:Catechols / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000378:metabolism*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology*
D002396:Catechols; D008996:Monoamine Oxidase Inhibitors; D013844:Thiazoles; D015102:3,4-Dihydroxyphenylacetic Acid; C063456:Ro 41-1049; D007980:Levodopa; C034221:catechol; D004298:Dopamine