三氟拉嗪和苯环利定对肌肉培养物中氨甲酰胆碱诱导的阳离子内流的协同抑制作用。

Synergistic inhibition by trifluoperazine and phencyclidine of carbamylcholine-induced cation influx in muscle cultures.

作者信息

Gamliel A, Schreiber G, Shainberg A

出版信息

Biochem Pharmacol. 1987 Jul 15;36(14):2271-7. doi: 10.1016/0006-2952(87)90590-9.

Abstract

The effect of trifluoperazine (TFP) and phencyclidine (PCP) on acetylcholine receptor (AChR) function was studied in rat myotubes differentiated in vitro. While both drugs exerted an inhibitory effect on carbamylcholine (CCh)-induced Na+ or Ca2+ flux (I50 = 5-9 microM), alpha-bungarotoxin (alpha-Bgt) binding was not affected. The inhibitory effect of both drugs was independent of CCh concentration. The mutual inhibitory effect of TFP and PCP on Ca2+ influx was analyzed using three alternative models of interaction between the two drugs: competitive, additive and synergistic inhibition models. Our results are in accord with a synergistic interaction between the drugs probably not through desensitization. This synergistic interaction between the drugs provides a biochemical rationale to the phenothiazine contraindication in the treatment of PCP psychosis.

摘要

在体外分化的大鼠肌管中研究了三氟拉嗪（TFP）和苯环己哌啶（PCP）对乙酰胆碱受体（AChR）功能的影响。虽然两种药物对氨甲酰胆碱（CCh）诱导的Na⁺或Ca²⁺通量均有抑制作用（半数抑制浓度I50 = 5 - 9 microM），但α-银环蛇毒素（α-Bgt）结合不受影响。两种药物的抑制作用均与CCh浓度无关。使用两种药物相互作用的三种替代模型：竞争性、相加性和协同抑制模型，分析了TFP和PCP对Ca²⁺内流的相互抑制作用。我们的结果符合药物之间的协同相互作用，可能不是通过脱敏作用。药物之间的这种协同相互作用为在治疗PCP精神病时使用吩噻嗪类药物的禁忌提供了生化依据。