Reversibility of the interaction of CGP 11305 A with MAO A in vivo.
The aim of this study was to resolve the apparent discrepancy between the short duration of action of the MAO inhibitory effect of CGP 11305 A in vivo and its irreversible interaction with the enzyme in vitro. When rats were treated with CGP 11305 A 2 h prior to clorgyline administration and MAO activity was determined 46 h thereafter, MAO A in brains and livers was protected from inhibition by clorgyline provided the dose relation was adequate. However, if clorgyline doses were equal to or higher than those of CGP 11305 A, there was only partial or no protection despite the fact that the doses of CGP 11305 A blocked MAO A nearly completely at the moment of clorgyline administration. Using a different approach, it was found that dopamine and serotonin released from their stores in rat striatum by tetrabenazine could displace CGP 11305 A from the MAO A active site in vivo, in contrast to clorgyline. These results suggest that the interaction of CGP 11305 A with MAO in vivo is reversible and competitive.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D003010:Clorgyline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013747:Tetrabenazine / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C038213:brofaromine; D008995:Monoamine Oxidase; D003010:Clorgyline; D004298:Dopamine; D006719:Homovanillic Acid; D013747:Tetrabenazine