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SYNOPSIS

We report the first use of ICI 169,369, a selective S2 receptor antagonist, in acute and prophylactic treatment of migraine.

Ten selected patients documented their migraine attacks over a 2-month period of open treatment with ICI 169,369, 30 mg orally, for acute therapy. They compared this treatment with others they had experience of. Four of these patients undertook a pharmacokinetic study comparing drug absorption in an acute attack to that when symptom-free. Prophylaxis was then commenced with the same drug, 30 mg bd. Patients recorded symptoms in diary cards noting the effects of treatment on the usual frequency and severity of their attacks.

The pharmacokinetic study showed that drug absorption could be markedly impaired during an acute attack. Nevertheless, in 35 attacks treated acutely, half the patients reported some efficacy apparent to them. One third of patients considered ICI 169,369 to be better treatment on this one occasion than their own usual medication. Some benefit was also noted during prophylaxis. There was a statistically significant reduction in attack frequency from the baseline observed during acute therapy only, but this was arguably compatible with placebo response.

S2 receptor antagonism may have some beneficial effect in acute or prophylactic treatment of migraine, but it is not marked and does not support S2 receptor activation being important in its pathogenesis.