The effects of (+)-UH232 and (-)-DS121 on local cerebral glucose utilization in rats.

Although (+)-UH232 (cis-(+)-5-methoxy-1-methyl-2-(n-dipropylamino)tetralin) and (-)-DS121 (S(-)-3-(3-(cyanophenyl)-N-n-propylpiperidine) are both preferential dopamine autoreceptor antagonists, (-)-DS121 is a more effective behavioral stimulant and dopamine releasing agent. To further compare these two agents, Sokoloff's 2-deoxyglucose autoradiography method was used to study the effects of (+)-UH232 and (-)-DS121 on regional brain energy metabolism. (+)-UH232, 30 mg/kg i.p., depressed metabolism in 37 of 65 brain regions and antagonized the stimulant effects of amphetamine. (-)-DS121, 30 mg/kg i.p., exhibited a strong, nonsignificant trend towards an increase in regional brain energy metabolism by itself and enhanced the stimulant effects of amphetamine. The data demonstrate dramatic differences in the effects of two autoreceptor antagonists on regional brain energy metabolism. It is concluded that, compared to (+)-UH232, (-)-DS121 is a more effective stimulant of brain energy metabolism and autoreceptor antagonist owing to its greater ability to increase DA release.