beta-Carboline-3-carboxylate-t-butyl ester: a selective BZ1 benzodiazepine receptor antagonist.
The effectiveness of beta-carboline-3-carboxylate-t-butyl ester (beta CCtB) in antagonizing the anticonvulsant, ataxic and antipunishment effects of diazepam were evaluated. In mice, beta CCtB at doses of 3 and 10 mg/kg produced a dose-related antagonism of the anticonvulsant effects of diazepam against pentylenetetrazole (80 mg/kg). A dose of 30 mg/kg of beta CCtB did not produce a further shift in the diazepam dose-effect curve, apparently because beta CCtB failed to block the muscle-relaxant effects of diazepam. Further, beta CCtB (30 mg/kg) failed to antagonize the ataxic effects of diazepam in an inverted screen test. Rats responded under a multiple schedule where in one component every twentieth response (FR20) resulted in water presentation (unpunished component) and in another component every twentieth response (FR20) resulted in both shock and water presentation (punished component). Diazepam p.o. (0.1 to 10 mg/kg) first increased and then decreased rates in the punished component but only decreased rates in the unpunished component. beta CCtB had no effect on response rates when administered alone, but antagonized the rate-increasing effects of diazepam in the punished component. beta CCtB did not alter the rate-decreasing effects of diazepam in either component. Thus, beta CCtB selectively antagonized the effects of diazepam on punished behavior as well as the anticonvulsant effects of diazepam, but beta CCtB failed to antagonize the rate-decreasing and ataxic effects of diazepam. These results are consistent with the interpretation that beta CCtB is a selective BZ1 benzodiazepine receptor antagonist.
D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors; D001259:Ataxia / Q000139:chemically induced / Q000517:prevention & control; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D001667:Binding, Competitive; D002243:Carbolines / Q000378:metabolism / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011678:Punishment; D051381:Rats; D011916:Rats, Inbred F344; D011963:Receptors, GABA-A / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D000927:Anticonvulsants; D002243:Carbolines; D007211:Indoles; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C043232:tert-butyl beta-carboline-3-carboxylate; D003975:Diazepam