Attenuation of haloperidol-induced catalepsy by a 5-HT2C 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-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.
Reavill
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Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, England.
Kettle
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A
Holland
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Riley
G
G
Blackburn
T P
TP
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control*; D002460:Cell Line; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005464:Fluorobenzenes / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*
D018492:Dopamine Antagonists; D005464:Fluorobenzenes; D007211:Indoles; D010880:Piperidines; D011804:Quinolines; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; C118948:SB 215505; D012702:Serotonin Antagonists; C079049:volinanserin; D006220:Haloperidol