Regular paperMixed agonist-antagonist properties of Umespirone (cas 107736-98-1) at neostriatal dopamine receptors in relation to its behavioral effects in the rat

Add time:08/17/2019    Source:sciencedirect.com

In normal rats treated with the inhibitor of cerebral decarboxylase, NSD-1015 (100 mg kg−1 i.p.), Umespirone (cas 107736-98-1) (1.9–30.0 μmol kg−1 s.c.) produced an increase in neostriatal DOPA (dihydroxyphenylalanine) accumulation, whereas decreased DOPA accumulation was obtained in reserpine-pretreated (5 mg kg−1 s.c., −18 h) animals. The latter effect was statistically significant only in the ventral, limbic, portion of the neostriatum. Neostriatal 5-hydroxytryptophan (5-HTP) accumulation was decreased in the reserpine-treated animals but not in normal controls. DOPA accumulation in the neocortex was not affected by umespirone treatment in either preparation, whereas 5-HTP accumulation was decreased in the reserpine-treated animals. Spontaneous locomotor activity was suppressed by umespirone at doses that did not affect treadmill locomotion (7.9–31.2 μmol kg−1 s.c., −30 min), and there were no signs of catalepsy at doses ranging from 31.2–249.6 μmol kg−1 s.c. up to 2 h after injection. Thus, umespirone behaves as a mixed dopamine receptor agonist/antagonist and also displays 5-HT receptor agonist properties. This biochemical profile was associated with sedation, as observed in the open-field, at doses which did not affect treadmill locomotion or induced catalepsy.

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