Mixed agonist-antagonist properties of umespirone at neostriatal dopamine receptors in relation to its behavioral effects in the rat.
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| Abstract |
In normal rats treated with the inhibitor of cerebral decarboxylase, NSD-1015 (100 mg kg-1 i.p.), umespirone (1.9-30.0 mumol 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 mumol kg-1 s.c., -30 min), and there were no signs of catalepsy at doses ranging from 31.2-249.6 mumol 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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| Authors | S Ahlenius, A Wijkström |
| Journal | European journal of pharmacology (Eur J Pharmacol) Vol. 222 Issue 1 Pg. 69-74 (Nov 03 1992) ISSN: 0014-2999 [Print] Netherlands |
| PMID | 1361441 (Publication Type: Journal Article) |
| Chemical References |
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