Hermann B, Wetzel C H, Pestel E, Zieglgänsberger W, Holsboer F, Rupprecht R
Clinical Institute, Max Planck Institute of Psychiatry, Munich, Germany.
Biochem Biophys Res Commun. 1996 Aug 23;225(3):957-60. doi: 10.1006/bbrc.1996.1278.
The atypical neuroleptic clozapine is thought to exert its psychopharmacological actions through a variety of neurotransmitter receptors. It binds preferentially to D4 and 5-HT2 receptors; however, little is known on it's interaction with the 5-HT3 receptor. Using a cell line stably expressing the 5-HT3 receptor, whole-cell voltage-clamp analysis revealed functional antagonistic properties of clozapine at low nanomolar concentrations in view of a binding affinity in the upper nanomolar range. Because the concentration of clozapine required for an interaction with the 5-HT3 receptor can be achieved with therapeutical doses, functional antagonistic properties at this ligand-gated ion channel may contribute to its unique psychopharmacological profile.
非典型抗精神病药物氯氮平被认为是通过多种神经递质受体发挥其精神药理作用的。它优先与D4和5-HT2受体结合；然而，关于它与5-HT3受体的相互作用却知之甚少。使用稳定表达5-HT3受体的细胞系，全细胞膜片钳分析显示，鉴于氯氮平在纳摩尔浓度上限的结合亲和力，它在低纳摩尔浓度下具有功能性拮抗特性。由于治疗剂量可以达到氯氮平与5-HT3受体相互作用所需的浓度，因此这种配体门控离子通道的功能性拮抗特性可能有助于其独特的精神药理特性。
