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.
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Authors | C Reavill, A Kettle, V Holland, G Riley, T P Blackburn |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 126
Issue 3
Pg. 572-4
(Feb 1999)
ISSN: 0007-1188 [Print] England |
PMID | 10188965
(Publication Type: Journal Article)
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Chemical References |
- Dopamine Antagonists
- Fluorobenzenes
- Indoles
- Piperidines
- Quinolines
- Receptor, Serotonin, 5-HT2A
- Receptor, Serotonin, 5-HT2B
- Receptor, Serotonin, 5-HT2C
- Receptors, Serotonin
- SB 215505
- Serotonin Antagonists
- volinanserin
- Haloperidol
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Topics |
- Animals
- Binding, Competitive
(drug effects)
- Catalepsy
(chemically induced, prevention & control)
- Cell Line
- Dopamine Antagonists
(pharmacology)
- Fluorobenzenes
(pharmacology)
- Haloperidol
(pharmacology)
- Humans
- Indoles
(pharmacology)
- Male
- Piperidines
(pharmacology)
- Quinolines
(pharmacology)
- Radioligand Assay
- Rats
- Rats, Sprague-Dawley
- Receptor, Serotonin, 5-HT2A
- Receptor, Serotonin, 5-HT2B
- Receptor, Serotonin, 5-HT2C
- Receptors, Serotonin
(drug effects, metabolism)
- Serotonin Antagonists
(pharmacology)
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