Pieri L, Biry P
Eur J Pharmacol. 1985 Jun 19;112(3):355-62. doi: 10.1016/0014-2999(85)90781-2.
Dose-response curves for the convulsant effect of isoniazid were determined in male rats. The specific benzodiazepine antagonist Ro 15-1788, at doses from 20 to 100 mg/kg i.v. or at 300 mg/kg p.o., failed to produce any relevant shift of the isoniazid dose-response curves to the left (proconvulsant) or to the right (anticonvulsant). In contrast, the benzodiazepine receptor ligand ethyl-beta-carboline-3-carboxylate (beta-CCE) 10 mg/kg i.v. produced a clear-cut shift to the left of the isoniazid dose-response curve. Ro 15-1788 was inactive up to high p.o. or i.v. doses, versus convulsions induced by a low supraliminal dose of isoniazid, whereas beta-CCE had a significant proconvulsant effect beginning at 5 mg/kg i.v. This effect of beta-CCE was dose dependently antagonized by Ro 15-1788. In conclusion, in the present experimental conditions Ro 15-1788 showed no inverse agonistic properties at benzodiazepine receptors, in contrast to beta-CCE.
在雄性大鼠中测定了异烟肼惊厥作用的剂量-反应曲线。特异性苯二氮䓬拮抗剂Ro 15 - 1788，静脉注射剂量为20至100mg/kg或口服剂量为300mg/kg时，未能使异烟肼剂量-反应曲线向左（促惊厥）或向右（抗惊厥）产生任何相关偏移。相比之下，苯二氮䓬受体配体β-CCE静脉注射10mg/kg可使异烟肼剂量-反应曲线明显左移。与异烟肼低阈上剂量诱导的惊厥相比，Ro 15 - 1788在高口服或静脉注射剂量下均无活性，而β-CCE静脉注射5mg/kg起就有显著的促惊厥作用。β-CCE的这种作用可被Ro 15 - 1788剂量依赖性拮抗。总之，在本实验条件下，与β-CCE相反，Ro 15 - 1788在苯二氮䓬受体上未表现出反向激动特性。
