Mice and rats are sensitized to the proconvulsant action of a benzodiazepine-receptor inverse agonist (FG 7142) following a single dose of lorazepam.
Rats and mice were treated with lorazepam (1.0 mg/kg) or its vehicle. Six h later seizure threshold to i.v. pentylenetetrazole was determined following treatment with the benzodiazepine-receptor inverse agonist FG 7142, the antagonist Ro 15-1788 or a second dose of lorazepam. Although lorazepam alone was anticonvulsant 6 h after its administration, animals pretreated with lorazepam were more sensitive to the proconvulsant action of FG 7142 and less sensitive to the effects of a second treatment with lorazepam.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D004347:Drug Interactions; D005442:Flumazenil; D007274:Injections, Intraperitoneal; D008140:Lorazepam / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors
D001570:Benzodiazepinones; D002243:Carbolines; D003292:Convulsants; D011963:Receptors, GABA-A; D005442:Flumazenil; C035874:FG 7142; D008140:Lorazepam