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Abstract
Based on the finding that VA-045, a novel apovincaminic acid derivative, had improved disturbance in consciousness, we examined the effects of the drug on the electrical activity of locus coeruleus (LC) neurons in animal models of consciousness disturbance. The animal models of consciousness disturbance used in this experiment were closed head injury (CHI) and intravenous injection of clonidine. CHI as well as clonidine injection reduced the spontaneous activity of LC neurons. The reduction of the spontaneus activity of LC neurons following CHI or clonidine injection was restored by intravenous injection of VA-045. The change of LC neuronal activity induced by VA-045 preceded desynchronization of EEG. These results suggest that VA-045 exerts its ameliorating effect on consciousness disturbance, at least in part, by augmenting the spontaneous activity of noradrenergic LC neurons.
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