Actions of midazolam in the spinal cord of the cat

Midazolam, which induces anaesthesia in humans at intravenous doses of 0.3 mg/kg, did not anaesthetize cats at doses of 20 mg/kg. Nevertheless, intravenous doses as small as 0.3 mg/kg enhanced spinal primary afferent depolarization and presynaptic inhibition of spinal monosynaptic reflexes, and both intravenous and microelectrophoretic administration of midazolam enhanced the inhibitory effect of GABA on spinal neurones and the depolarization of Ia afferent terminations by GABA and piperidine-4-sulphonate. Some degree of specificity was demonstrated for the inhibitory effect of GABA in relation to those of glycine and noradrenaline, and the enhancement by midazolam of inhibition by GABA was blocked by R015-1788, which alone was inactive. Although these results are consistent with proposals that depressant benzodiazepines enhance the effectiveness of GABA as a central transmitter, such an effect alone may not fully account for the anaesthesia produced by midazolam in humans.