beta-Carboline-3-carboxylic acid ethyl ester antagonizes diazepam activity.
Analogous to the progression of events in the opiate receptor-enkaphalin area, the first reports that benzodiazepines have selective and specific high-affinity binding sites in brain have stimulated a search for the endogenous 'ligand' or substance that might normally act at these sites. Braestrup and co-workers have extracted from human urine a gamma-fraction (ref. 10) which they have recently identified as beta-carboline-3-carboxylic acid ethyl ester (beta CEE). They reported that this substance is extremely potent in displacing 3H-diazepam from brain binding sites and proposed that a beta-carboline-3-carboxylic acid derivative might, in part, be the endogenous ligand for the brain benzodiazepine receptor. We have examined several synthetically derived beta-carboline-3-carboxylic acid analogues and now present data obtained from testing only the beta CEE described by Braestrup et al. In addition to confirming these workers' observation that this compound is a potent displacer of 3H-diazepam from brain tissue, our pharmacological data indicate that beta CEE has activity that is opposite to, rather than similar to, that of diazepam.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002243:Carbolines / Q000494:pharmacology*; D003975:Diazepam / Q000037:antagonists & inhibitors*; D004357:Drug Synergism; D007211:Indoles / Q000494:pharmacology*; D008566:Membranes / Q000378:metabolism; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A; D012640:Seizures / Q000139:chemically induced
D002243:Carbolines; D007211:Indoles; D011955:Receptors, Drug; D011963:Receptors, GABA-A; C024915:beta-carboline-3-carboxylic acid ethyl ester; D003975:Diazepam; D010433:Pentylenetetrazole