Application of metoclopramide specificity in migraine attacks therapy

The 5-HT3 antagonism property of metoclopramide, acting on receptors presumably located in the trigeminovascular system, is the theoretical basis of its remarkable success, as a single intravenous agent, in the treatment of migraine attacks. The specific anti-migraine activity of oral metoclopramide is, most probably, applicable only when its plasma level is equivalent to 10 mg injected intravenously. The clinical effective dose of ergotamine, beginning from the minimal dose of 1 mg, correlates well with its affinity for 5-HT1B and 5-HT1D receptors, and the rank order of clinical potency of ergotamine is superior to sumatriptan. The presumed synergic power of drugs that interact with both 5-HT1 and 5-HT3 receptors is examined, in order to formulate a highly potent, low headache recurrence, oral combination.