A-68930, a novel potent dopamine D1 receptor agonist

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Abstract
A-68930 [1R,3S)-1-aminomethyl-5,6-dihydroxy-3-phenylisochroman HCI] is a novel, potent and selective dopamine D1 receptor agonist. Previous reports have shown that the selective D1 partial agonist, SK&F 38393, reduced food consumption in rats and mice. The aim of this study was to undertake a microstructural analysis of the effects of A-68930 on food intake and feeding behaviour in non-deprived male rats trained to consume a highly palatable diet in a 20 min period. A-68930 (0.1–1.0 mg/kg, s.c.) produced a dose-dependent reduction in food intake, which was due to a reduction in the frequency of bouts of feeding but not to a reduction in bout duration. A-68930 had little effect on the latency to initiate feeding or on the local rate of eating. Hence, it had a selective action on the parameters of eating, which is distinctly different from the effects of selective D2 agonists or of indirectly acting psychomotor stimulants like cocaine. A-68930 also increased grooming by lengthening the grooming bouts, and reduced locomotion and rearing responses. At the largest dose, immobility was increased. The anorectic effect of A-68930 may reflect, at least in part, the increased grooming it produces.

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