Mizoule J, Rataud J, Uzan A, Mazadier M, Daniel M, Gauthier A, Ollat C, Gueremy C, Renault C, Dubroeucq M C
Arch Int Pharmacodyn Ther. 1984 Oct;271(2):189-97.
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.
PK 8165是一种新型喹啉衍生物，对脑型苯二氮䓬结合位点具有良好的亲和力，并且在Vogel试验中具有抗冲突活性。然而，与经典苯二氮䓬类药物（BZ）不同的是，该化合物没有抗惊厥和镇静特性。由于生化研究表明PK 8165是BZ受体的部分激动剂，因此研究了它与地西泮（DZ）的惊厥、镇静和肌肉松弛特性之间的相互作用。PK 8165（腹腔注射12.5至50mg/kg）增强了DZ对小鼠最大电休克（M.E.S.）诱发惊厥和电击诱发争斗的拮抗作用。此外，PK 8165在相同剂量范围内增强了DZ对小鼠的肌肉松弛和催眠作用。这些增强作用具有特异性，因为PK 8165不干扰苯巴比妥和甲己炔巴比妥对小鼠M.E.S.和翻正反射的作用。此外，PK 8165的抗冲突活性（口渴大鼠的罚饮）被中枢活性BZ的特异性拮抗剂RO15 - 1788所拮抗。
