Antagonism of cocaine's pharmacological effects by the stimulant dopaminergic antagonists, (+)-AJ76 and (+)-UH232
by
Piercey MF, Lum JT, Hoffmann WE,
Carlsson A, Ljung E, Svensson K
Upjohn Co., Kalamazoo, MI 49001.
Brain Res 1992 Aug 21;588(2):217-22
ABSTRACTThe aminotetralins (+)-AJ76 and (+)-UH232 are stimulant dopaminergic antagonists, which may preferentially antagonize autoreceptors of dopamine nerve terminals. Both agents antagonized cocaine's depressant effects on firing rates of ventral tegmental dopaminergic neurons, but (+)-UH232 was much more potent. When injected simultaneously with cocaine, (+)-UH232 inhibited and (+)-AJ76 enhanced the locomotor stimulation observed during the first 30 min following s.c. cocaine administration. However, (+)-AJ76 antagonized cocaine-induced stereotypies as well as the later more intense cocaine locomotor stimulation. It is suggested that preferential dopamine autoreceptor antagonists may provide a novel approach to a pharmacotherapy for treating cocaine abuse.GBR12909
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