Ahlenius S, Wijkström A
Department of Behavioral Pharmacology, Astra Arcus AB, Södertälje, Sweden.
Eur J Pharmacol. 1992 Nov 3;222(1):69-74. doi: 10.1016/0014-2999(92)90464-f.
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.
在用脑脱羧酶抑制剂NSD - 1015（100毫克/千克，腹腔注射）处理的正常大鼠中，乌美螺酮（1.9 - 30.0微摩尔/千克，皮下注射）使新纹状体中左旋多巴（二羟基苯丙氨酸）蓄积增加，而在利血平预处理（5毫克/千克，皮下注射，-18小时）的动物中左旋多巴蓄积减少。后一种效应仅在新纹状体腹侧边缘部分具有统计学意义。在利血平处理的动物中，新纹状体5 - 羟色氨酸（5 - HTP）蓄积减少，但在正常对照中未减少。在两种制备中，乌美螺酮处理均不影响新皮质中左旋多巴的蓄积，而在利血平处理的动物中5 - HTP蓄积减少。乌美螺酮在不影响跑步机运动的剂量（7.9 - 31.2微摩尔/千克，皮下注射，-30分钟）下抑制自发运动活动，并且在注射后长达2小时内，在31.2 - 249.6微摩尔/千克，皮下注射的剂量范围内没有僵住症的迹象。因此，乌美螺酮表现为多巴胺受体激动剂/拮抗剂的混合物，并且还表现出5 - HT受体激动剂特性。这种生化特征与在旷场试验中观察到的镇静作用相关，在不影响跑步机运动或诱发僵住症的剂量下。
