The effects of a new water soluble benzodiazepine RO-21-3981 on responses of spinal neurones in the pentobarbitone anaesthetised cat to acetylcholine, and the amino acid analogues N-methyl-D-aspartate and kainate were determined using the microiontophoretic technique. RO-21-3981 reduced the sensitivity of neurones to all three excitants. However, on spinal Renshaw cells iontophoretic RO-21-3981 reduced acetylcholine responses more than amino acid responses. Administered intravenously RO-21-3981 depressed dorsal root but not ventral root evoked responses of Renshaw cells. The possible mechanism responsible for the effects of RO-21-3981 are discussed. Within the mammalian central nervous system iontophoretically administered benzodiazepines have been studied mostly in respect of their interaction with the inhibitory amino acids GABA and glycine (Curtis, Game and Lodge, 1976; Curtis, Lodge, Johnston and Brand, 1976; Dray and Straughan, 1976; Steiner and Felix, 1976; Kozhechkin and Ostrovskaya, 1977). However, a recent study on the isolated frog spinal cord suggests that benzodiazepines may also interact with excitatory amino acids (Evans, Francis and Watkins, 1977). Hence, the present experiments describe the effect of a new water soluble benzodiazepine, RO-21-3981, administered iontophoretically on the excitatory responses of Renshaw cells and other spinal interneurones to acetylcholine and/or kainate and N-methyl-D-aspartate (NMDA). The latter two substances are potent analogues of L-glutamate and L-aspartate respectively. In addition, the effects of intravenously administered RO-21-3981 on synaptic responses of Renshaw cells evoked by ventral and dorsal root stimulation were investigated.
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