在5-HT1A受体激动剂和拮抗剂的抗精神病药物:[35 s] GTPgammaS绑定的研究。
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Newman-Tancredi, Gavaudan年代,孔蒂C, Chaput C, Touzard M, Verriele L,文澜Audinot V,乔丹
在5-HT1A受体激动剂和拮抗剂的抗精神病药物:[35 s] GTPgammaS绑定的研究。
欧元J杂志。1998年8月21日,355 (2):245 - 56。
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9760039 (在PubMed]
- 文摘
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重组体人(h) 5-HT1A受体介导转染的细胞膜蛋白激活特征在中国仓鼠卵巢(CHO)细胞利用guanosine-5 - o - (3 - (35 s)含硫的)三磷酸([35 s] GTPgammaS绑定)。的效力和有效性21 5 -受体受体激动剂和拮抗剂。受体激动剂,5-CT (carboxamidotryptamine)和flesinoxan显示高亲和力(subnanomolar Ki值)和高功效(Emax > 90%,相对于5 - = 100%)。相比之下,ipsapirone zalospirone和丁螺环酮显示部分激动剂活性。EC50s对兴奋剂的刺激(35 s] GTPgammaS绑定相关从竞争与Ki值绑定(r = + 0.99)。化合物检测拮抗剂中活动,methiothepin和(+)butaclamol表现出反兴奋剂的行为,抑制基底(35 s] GTPgammaS绑定。17个抗精神病药物的行为进行调查。氯氮平和几个公认的非典型抗精神病药物,包括齐拉西酮,奎硫平和tiospirone,展出部分激动剂活性和标记在h5-HT1A受体亲和力,类似于他们的hD2多巴胺受体的亲和力。相比之下,利培酮和sertindole显示低亲和力h5-HT1A受体和表现为“中性”对手,抑制5-HT-stimulated [35 s] GTPgammaS绑定。同样的“典型”精神安定剂,氟哌啶醇,号,raclopride和氯丙嗪表现出相对较低的亲和力和“中性”h5-HT1A受体拮抗剂活动与Ki值与各自Kb值。 The present data show that (i) [35S]GTPgammaS binding is an effective method to evaluate the efficacy and potency of agonists and antagonists at recombinant human 5-HT1A receptors. (ii) Like clozapine, several putatively 'atypical' antipsychotic drugs display balanced serotonin h5-HT1A/dopamine hD2 receptor affinity and partial agonist activity at h5-HT1A receptors. (iii) Several 'typical' and some putatively 'atypical' antipsychotic agents displayed antagonist properties at h5-HT1A sites with generally much lower affinity than at hD2 dopamine receptors. It is suggested that agonist activity at 5-HT1A receptors may be of utility for certain antipsychotic agents.