Peripheral metabolism of beta-carboline-carboxylic acid esters.
Esters of beta-carboline-3-carboxylic acid have recently been identified as potent inhibitors of brain benzodiazepine receptors in vitro. Ethyl beta-carboline-3-carboxylate (beta-CCE), however, is a rather weak inhibitor in vivo of benzodiazepine receptors in mice. The ED50-value was 91 mg/kg intraperitoneally 35 min after administration (ED50 is that dose which inhibits by 50% the specific binding of 3H-flunitrazepam intravenously). ED50 for beta-CCE was 2-20 fold lower in mice pretreated with organophosphorus esterase inhibitors, concomitantly with the observation of strong inhibition of liver and kidney hydrolyzing activity, using 3H-propyl beta-carboline-3-carboxylate as substrate. The rat brain contains only approximately 0.1% of the hydrolyzing activity as compared to the liver. It is concluded that some esters of beta-carboline-3-carboxylate exhibit only weak effects on benzodiazepine receptors in living animals due to hydrolysis outside the brain.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002243:Carbolines / Q000378:metabolism*; D004950:Esterases / Q000037:antagonists & inhibitors; D007211:Indoles / Q000378:metabolism*; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000187:drug effects*; D011963:Receptors, GABA-A
D002243:Carbolines; D007211:Indoles; D008024:Ligands; D011955:Receptors, Drug; D011963:Receptors, GABA-A; C024915:beta-carboline-3-carboxylic acid ethyl ester; D004950:Esterases