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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

5-HT2A receptor antagonist properties of cyamemazine in rat and guinea pig smooth muscle.

5-HT(2A) receptor antagonism seems to explain the low incidence of extrapyramidal side effects with atypical neuroleptics. Whether the neuroleptic cyamemazine, which at low doses is also devoid of extrapyramidal side effects, possesses 5-HT(2A) receptor antagonist properties is unknown. Cyamemazine was tested for its ability to antagonize 5-HT(2A)-mediated responses in isolated rat aorta and guinea pig trachea and to displace [3H]ketanserin specifically bound to rat brain membranes. In isolated rat aorta, cyamemazine potently and competitively antagonized serotonin-dependent contractions (pA(2)=8.82+/-0.26, n=7; Schild's slope=1.02+/-0.29). In this test, cyamemazine was of similar potency as ketanserin (pA(2)=8.23). In isolated guinea pig trachea, cyamemazine reduced maximum contractile responses to serotonin with pIC(50)=7.92+/-0.35, (n=4), whereas ketanserin exhibited a pIC(50)=8.79. Finally, cyamemazine displaced [3H]ketanserin specifically bound to rat brain membranes with pK(i)=8.76+/-0.53 (n=3). In conclusion, cyamemazine behaves as a potent antagonist at 5-HT(2A) receptors, which compares well with the reference compound, ketanserin. Whether this 5-HT(2A) receptor antagonist action of cyamemazine can explain its low incidence of extrapyramidal side effects deserves further investigation.[1]


  1. 5-HT2A receptor antagonist properties of cyamemazine in rat and guinea pig smooth muscle. Alvarez-Guerra, M., Hameg, A., Bayle, F., Dib, M., Garay, R.P. Eur. J. Pharmacol. (2002) [Pubmed]
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