Attenuation of haloperidol‐induced catalepsy by a 5‐HT2C receptor antagonist

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Abstract
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.British Journal of Pharmacology (1999) 126, 572–574; doi:10.1038/sj.bjp.0702350