D1受体拮抗剂SCH 23390与中枢5-羟色胺系统的相互作用：放射性配体结合研究、生化参数测定及对L-5-羟色氨酸综合征的影响

Interaction of the D1 receptor antagonist SCH 23390 with the central 5-HT system: radioligand binding studies, measurements of biochemical parameters and effects on L-5-HTP syndrome.

作者信息

Bischoff S, Heinrich M, Krauss J, Sills M A, Williams M, Vassout A

机构信息

Research Department, CIBA-GEIGY, Basel.

出版信息

J Recept Res. 1988;8(1-4):107-20. doi: 10.3109/10799898809048981.

DOI:10.3109/10799898809048981

PMID:3290470

Abstract

The interaction of SCH 23390 with dopamine (DA) and serotonin (5-HT) systems has been examined in vivo and in vitro. Like selective 5-HT2 blockers, SCH 23390 inhibited in vivo [3H]spiperone binding in the rat frontal cortex (ID50: 1.5 mg/kg) without interacting at D2 sites. SCH 23390 was equipotent to cinanserin and methysergide. In vitro, SCH 23390 inhibited [3H]ketanserin binding to 5-HT2 sites (IC50 = 30 nM). Biochemical parameters linked to DA and 5-HT were not changed excepted in striatum where SCH 23390 increased HVA and DOPAC. In the L-5-HTP syndrome model, SCH 23390 clearly showed antagonism of 5-HT2 receptors. SCH 23390 had weak affinity for 5-HT1B (IC50 = 0.5 microM), 5-HT1A (IC50 = 2.6 microM) and alpha 1-adrenergic receptors (IC50 = 4.4 microM).

摘要

已在体内和体外研究了 SCH 23390 与多巴胺（DA）和 5-羟色胺（5-HT）系统的相互作用。与选择性 5-HT2 阻滞剂一样，SCH 23390 在不与 D2 位点相互作用的情况下，抑制大鼠额叶皮质中体内[3H]螺哌隆结合（半数抑制剂量：1.5 毫克/千克）。SCH 23390 与辛那色林和甲基麦角新碱等效。在体外，SCH 23390 抑制[3H]酮色林与 5-HT2 位点的结合（半数抑制浓度 = 30 纳摩尔）。除纹状体中 SCH 23390 增加高香草酸（HVA）和 3,4-二羟基苯乙酸（DOPAC）外，与 DA 和 5-HT 相关的生化参数未发生变化。在 L-5-羟色氨酸（L-5-HTP）综合征模型中，SCH 23390 明显显示出对 5-HT2 受体的拮抗作用。SCH 对 5-HT1B（半数抑制浓度 = 0.5 微摩尔）、5-HT1A（半数抑制浓度 = 2.6 微摩尔）和α1-肾上腺素能受体（半数抑制浓度 = 4.4 微摩尔）具有较弱的亲和力。