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潜在抗精神病药物利姆卡唑(BW 234U)对大鼠A9和A10多巴胺能神经元的急性和亚慢性影响。

Acute and subchronic effects of Rimcazole (BW 234U), a potential antipsychotic drug, on A9 and A10 dopamine neurons in the rat.

作者信息

Piontek J A, Wang R Y

出版信息

Life Sci. 1986 Aug 18;39(7):651-8. doi: 10.1016/0024-3205(86)90047-0.

Abstract

The effects of acute and subchronic Rimcazole administration on A9 and A10 dopamine (DA) neurons were examined using extracellular single cell recording techniques. Intravenous injections of Rimcazole did not prevent or reverse the inhibition of firing rates of DA cells produced by DA agonist apomorphine (APO). Single intraperitoneal injection of Rimcazole decreased the number of spontaneously active DA cells in A10, but not in A9; it had no effect on the firing rate of DA neurons in either A9 or A10. Following prolonged administration of Rimcazole, 25 mg/kg/day for 28 days, there was a significant increase in the number of spontaneously active A10 DA neurons, but not A9 DA cells. The firing rate of both A9 and A10 DA cells decreased significantly following prolonged Rimcazole administration; however, the firing pattern of these cells did not change. In addition, chronic Rimcazole did not affect the ID50 of APO for DA neurons. These results suggest that Rimcazole has an indirect effect on DA neurons with a relative selectivity for A10 DA cells; it does not exhibit pharmacological profiles of previously reported antipsychotic drugs.

摘要

使用细胞外单细胞记录技术研究了急性和亚慢性给予利姆卡唑对A9和A10多巴胺(DA)神经元的影响。静脉注射利姆卡唑不能预防或逆转DA激动剂阿扑吗啡(APO)对DA细胞放电率的抑制作用。单次腹腔注射利姆卡唑可减少A10中自发活动的DA细胞数量,但对A9中的细胞数量无影响;它对A9或A10中DA神经元的放电率均无影响。在长时间给予利姆卡唑(25mg/kg/天,持续28天)后,自发活动的A10 DA神经元数量显著增加,但A9 DA细胞数量未增加。长时间给予利姆卡唑后,A9和A10 DA细胞的放电率均显著降低;然而,这些细胞的放电模式没有改变。此外,慢性给予利姆卡唑不影响APO对DA神经元的半数抑制剂量(ID50)。这些结果表明,利姆卡唑对DA神经元有间接作用,对A10 DA细胞具有相对选择性;它不表现出先前报道的抗精神病药物的药理学特征。

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