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Is migraine prophylactic activity caused by 5-HT2B or 5-HT2C receptor blockade?
1Preclinical Research Sandoz Pharma Ltd, Basel, Switzerland.
Abstract:
It has been suggested that activation of 5-HT2C receptors is involved in the initiation of a migraine attack. The 5-HT2C receptor and the newly cloned rat fundus 5-HT2B receptor show close pharmacological and structural resemblance. Antagonist pA2 values from the rat stomach and pKD values from a 5-HT2C receptor binding assay correlated both highly significantly (p < 0.005) with the daily dose of eight migraine prophylactic compounds. Although the small difference in antimigraine potency between the enantiomers of propranolol agrees with the lack of stereo-selectivity found on the rat fundus 5-HT2B receptor but not with the 5-HT2C receptor, the evidence available does not allow one to distinguish between 5-HT2C and 5-HT2B receptor blockade as possible mechanisms for prophylactic activity.