Rao T S, Cler J A, Mick S J, Dilworth V M, Contreras P C, Iyengar S, Wood P L
CNS Diseases Research, G.D. Searle & Co., Monsanto Company, St Louis, Missouri 63198.
Neuropharmacology. 1990 Dec;29(12):1191-7. doi: 10.1016/0028-3908(90)90044-r.
Opipramol, a tricyclic antidepressant drug, potently interacted with sigma recognition sites labelled by 3H-3-hydroxyphenyl)N-(1-propyl)piperidine ( 3H-3-PPP) with a Ki value of 50 +/- 8 nM and with minimal affinity for phencyclidine receptors (Ki greater than 30,000 nM). Opipramol potently increased the metabolism of dopamine in the striatum, olfactory tubercle and pyriform cortex of the rat and increased the release of dopamine from the striatum of the mouse, as measured by increases in the levels of 3-methoxytyramine in vivo. Opipramol increased plasma prolactin in the rat, only at a dose as large as 50 mg/kg dose. Irreversible inactivation of dopamine receptors by EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) did not affect the opipramol-induced increases in levels of dihydroxyphenylacetic acid (DOPAC) in the striatum of the rat, indicating a predominant role of activation of sigma receptors in the dopaminergic effects of opipramol. However, pretreatment with the putative sigma ligand, rimcazole, markedly potentiated the ability of opipramol to increase the metabolism of release of DA in the striatum of the mouse in vivo. These results suggest that rimcazole and opipramol interact at two distinct receptors, the pharmacological significance of which is yet to be elucidated.
奥匹哌醇是一种三环类抗抑郁药，能与由3H-3-羟基苯基)N-(1-丙基)哌啶[(3H-3-PPP)]标记的σ识别位点发生强烈相互作用，其Ki值为50±8 nM，对苯环己哌啶受体的亲和力极小（Ki大于30,000 nM）。奥匹哌醇能显著增加大鼠纹状体、嗅结节和梨状皮质中多巴胺的代谢，并增加小鼠纹状体中多巴胺的释放，这可通过体内3-甲氧基酪胺水平的升高来衡量。奥匹哌醇仅在高达50 mg/kg的剂量下才会增加大鼠血浆催乳素水平。EEDQ（N-乙氧基羰基-2-乙氧基-1,2-二氢喹啉）对多巴胺受体的不可逆失活并不影响奥匹哌醇诱导的大鼠纹状体中二羟基苯乙酸（DOPAC）水平的升高，这表明σ受体的激活在奥匹哌醇的多巴胺能效应中起主要作用。然而，用假定的σ配体利姆卡唑预处理可显著增强奥匹哌醇在体内增加小鼠纹状体中多巴胺代谢或释放的能力。这些结果表明利姆卡唑和奥匹哌醇在两种不同的受体上相互作用，其药理学意义尚待阐明。
