Newman-Tancredi A, Chaput C, Gavaudan S, Verrièle L, Millan M J
Department of Psychopharmacology, Institut de Recherches Servier, Paris, France.
Neuropsychopharmacology. 1998 May;18(5):395-8. doi: 10.1016/S0893-133X(97)00169-3.
It has been proposed that the arylalkylamine, (-)pindolol, potentiates the therapeutic action of antidepressant drugs in humans by blockade of 5-HT1A autoreceptors. Its interactions at human 5-HT1A receptors have not, however, been directly characterized. Herein, we demonstrate that (-)pindolol exhibits nanomolar affinity at human 5-HT1A receptors expressed in Chinese Hamster Ovary cells (CHO-h5-HT1A; Ki = 6.4 nmol/L). In a functional test of receptor-mediated G-protein activation (stimulation of [35S]-GTP gamma S binding) (-)pindolol displays an efficacy of 20.3% relative to the endogenous agonist, 5-HT (= 100%). (-)Pindolol also antagonizes 5-HT (100 nmol/L)-stimulated [35S]-GTP gamma S binding, reducing it to 19.8% of control binding. These data indicate that (-)pindolol acts as a (weak) partial agonist at CHO-h5-HT1A receptors and that it blocks the action of 5-HT at these sites.
有人提出，芳基烷基胺（-）吲哚洛尔可通过阻断5-HT1A自身受体来增强抗抑郁药物在人体内的治疗作用。然而，其与人5-HT1A受体的相互作用尚未得到直接表征。在此，我们证明（-）吲哚洛尔对中国仓鼠卵巢细胞（CHO-h5-HT1A）中表达的人5-HT1A受体表现出纳摩尔亲和力（Ki = 6.4 nmol/L）。在受体介导的G蛋白激活功能试验（刺激[35S]-GTPγS结合）中，相对于内源性激动剂5-HT（= 100%），（-）吲哚洛尔的效能为20.3%。（-）吲哚洛尔还拮抗5-HT（100 nmol/L）刺激的[35S]-GTPγS结合，将其降低至对照结合的19.8%。这些数据表明，（-）吲哚洛尔在CHO-h5-HT1A受体上作为（弱）部分激动剂起作用，并且它在这些位点阻断5-HT的作用。
