Pharmacological evidence that PK 8165 behaves as a partial agonist of brain type benzodiazepine receptors.
PK 8165, a new quinoline derivative, has a good affinity for brain type benzodiazepine binding sites and an anticonflict activity in the Vogel Test. However, contrarily to classical benzodiazepines (BZ) this compound is devoid of anticonvulsant and sedative properties. As biochemical studies suggested that PK 8165 is a partial agonist for BZ receptors, its interactions with convulsant, sedative and muscle relaxant properties of diazepam (DZ) were investigated. PK 8165 potentiates (12.5 to 50 mg/kg i.p.) the antagonistic effect of DZ on M.E.S.-induced seizures and footshock-induced fighting in mice. Moreover, PK 8165 potentiates in the same dose range the muscle relaxant and hypnotic effects of DZ in mice. These potentiations are specific since PK 8165 does not interfere with phenobarbital and mebubarbital effects in M.E.S. and righting reflex in mice. Also, PK 8165's anticonflict activity (punished drinking in thirsty rats) is antagonized by RO15-1788, a specific antagonist of centrally active BZ.
D000374:Aggression / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects; D005442:Flumazenil; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010634:Phenobarbital / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects
D000927:Anticonvulsants; D001570:Benzodiazepinones; D011804:Quinolines; D011963:Receptors, GABA-A; D005442:Flumazenil; C030078:pipequaline; D003975:Diazepam; D010634:Phenobarbital