In a double-blind crossover study, 8 patients with classical migraine received disulfiram (400 mg/day) for 6 days, alternating with matched placebo tablets at 2 weekly intervals. Intravenous dopamine and tyramine pressor tests were performed on the 3rd and 6th days of each phase, respectively. 50-75% of patients experienced migraine attacks within 24 h of a test. There was no difference in the incidence of attacks between dopamine and tyramine injections. The number of migraine-free days was more during the placebo week than during disulfiram treatment (p < 0.05). The post-tyramine migraine index correlated directly with the amount of tyramine administered during the dose-response test (r = 0.66), but no such relationship was found with dopamine. In a further study, post-tyramine migraine was observed in only 1 of 5 patients treated with propranolol (80 mg/day) for 4 weeks. Neither disulfiram nor propranolol influenced the tyramine pressor sensitivity. It is concluded that increased adrenergic activity is responsible for more frequent attacks during disulfiram medication. A similar mechanism probably is responsible for post-dopamine/tyramine migraine in susceptible subjects. It is unlikely that tyramine plays any specific role, except via its effect on the adrenergic system, in the pathogenesis of migraine attacks. However, the tyramine challenge test can be useful in the evaluation of a putative antimigranous activity of a new drug.

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