Attenuation of haloperidol‐induced catalepsy by a 5‐HT 2C receptor antagonist

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‐HT 2 than for dopamine D 2 receptors. Our aim was to identify which 5‐HT 2 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‐HT 2A , 5‐HT 2B and 5‐HT 2C receptors expressed in Human Embryo Kidney (HEK293) cells. Haloperidol (1.13 mg kg −1 i.p.) induced catalepsy in all experiments. The selective 5‐HT 2C/2B receptor antagonist, SB‐228357 (0.32–10 mg kg −1 p.o.) significantly reversed haloperidol‐induced catalepsy whereas the 5‐HT 2A and 5‐HT 2B 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‐HT 2C receptors in the anticataleptic action of SB‐228357. British Journal of Pharmacology (1999) 126 , 572–574; doi: 10.1038/sj.bjp.0702350