The depressant effect of GYKI 52466 on spinal reflex transmission in rats is mediated via non-NMDA and benzodiazepine receptors.

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.