Block F, Schwarz M
Department of Neurology, University of Essen, Germany.
Eur J Pharmacol. 1994 Apr 21;256(2):149-53. doi: 10.1016/0014-2999(94)90239-9.
The present study examined the mechanisms by which GYKI 52466 (1-(amino-phenyl)-4-methyl-7,8-methyldioxy-5H-2,3-benzodiazepine) exerts its muscle relaxant effects. Intrathecal injection of the specific N-methyl-D-aspartate (NMDA) receptor antagonist (-)-2-amino-7-phosphonoheptanoate (AP7, 50-500 nmol) and systemic application of the benzodiazepine diazepam (0.2-5 mg/kg) dose dependently reduced the integrated area of the polysynaptic flexor reflex without affecting the monoxynaptic H-reflex. In contrast, intrathecal administration of the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX, 0.1-10 nmol) depressed the H-reflex in a dose-dependent manner without affecting the flexor reflex. The depressant effect of GYKI 52466 on the flexor reflex was reduced by coadministration with flumazenil (5 mg/kg i.p.), an antagonist at the benzodiazepine receptor, whereas coadministration of the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-tertbutyl-4-isoxazole-propionic acid (ATPA, 0.1 pmol) with GYKI 52466 attenuated the reduction of the H-reflex induced by GYKI 52466. The chosen doses of flumazenil and ATPA did not affect spinal reflex transmission when given alone. These data suggest that GYKI 52466 depresses spinal reflex transmission via an action on non-NMDA receptors and on benzodiazepine receptors.
本研究探讨了GYKI 52466（1-（氨基苯基）-4-甲基-7,8-亚甲二氧基-5H-2,3-苯并二氮杂卓）发挥肌肉松弛作用的机制。鞘内注射特异性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（-）-2-氨基-7-膦酰庚酸（AP7，50 - 500 nmol）以及全身应用苯二氮卓类地西泮（0.2 - 5 mg/kg）均剂量依赖性地减少了多突触屈肌反射的积分面积，而不影响单突触H反射。相反，鞘内注射非NMDA受体拮抗剂6,7-二硝基喹喔啉-2,3-二酮（DNQX，0.1 - 10 nmol）则剂量依赖性地抑制H反射，而不影响屈肌反射。与苯二氮卓受体拮抗剂氟马西尼（5 mg/kg腹腔注射）共同给药可减弱GYKI 52466对屈肌反射的抑制作用，而将非NMDA受体激动剂α-氨基-3-羟基-5-叔丁基-4-异恶唑丙酸（ATPA，0.1 pmol）与GYKI 52466共同给药则可减弱GYKI 52466诱导的H反射降低。单独给予所选剂量的氟马西尼和ATPA时不影响脊髓反射传递。这些数据表明，GYKI 52466通过作用于非NMDA受体和苯二氮卓受体来抑制脊髓反射传递。
