Reavill C, Kettle A, Holland V, Riley G, Blackburn T P
Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, England.
Br J Pharmacol. 1999 Feb;126(3):572-4. doi: 10.1038/sj.bjp.0702350.
Atypical neuroleptics produce fewer extrapyramidal side-effects (EPS) than typical neuroleptics. The pharmacological profile of atypical neuroleptics is that they have equivalent or higher antagonist affinity for 5-HT2 than for dopamine D2 receptors. Our aim was to identify which 5-HT2 receptor contributed to the atypical profile. Catalepsy was defined as rats remaining immobile over a horizontal metal bar for at least 30 s, 90 min after dosing. Radioligand binding assays were carried out with homogenates of human recombinant 5-HT2A, 5-HT2B and 5-HT2C receptors expressed in Human Embryo Kidney (HEK293) cells. Haloperidol (1.13 mg kg(-1) i.p.) induced catalepsy in all experiments. The selective 5-HT2C/2B receptor antagonist, SB-228357 (0.32-10 mg kg(-1) p.o.) significantly reversed haloperidol-induced catalepsy whereas the 5-HT2A and 5-HT2B receptor antagonists, MDL-100907 (0.003-0.1 mg kg(-1) p.o.) and SB-215505 (0.1-3.2 mg kg(-1) p.o.) respectively did not reverse haloperidol-induced catalepsy. The data suggest a role for 5-HT2C receptors in the anticataleptic action of SB-228357.
非典型抗精神病药物比典型抗精神病药物产生的锥体外系副作用（EPS）更少。非典型抗精神病药物的药理学特征是它们对5-羟色胺2（5-HT2）的拮抗剂亲和力与或高于对多巴胺D2受体的亲和力。我们的目的是确定哪种5-HT2受体促成了非典型特征。僵住症定义为给药90分钟后大鼠在水平金属棒上保持不动至少30秒。用在人胚肾（HEK293）细胞中表达的重组人5-HT2A、5-HT2B和5-HT2C受体的匀浆进行放射性配体结合试验。在所有实验中，氟哌啶醇（1.13毫克/千克腹腔注射）均诱发僵住症。选择性5-HT2C/2B受体拮抗剂SB-228357（0.32 - 10毫克/千克口服）能显著逆转氟哌啶醇诱发的僵住症，而5-HT2A和5-HT2B受体拮抗剂MDL-100907（0.003 - 0.1毫克/千克口服）和SB-215505（0.1 - 3.2毫克/千克口服）分别不能逆转氟哌啶醇诱发的僵住症。数据表明5-HT2C受体在SB-228357的抗僵住症作用中发挥作用。
