Relationships between headache and amine changes after administration of reserpine to migrainous patients.

There is evidence that spontaneous migraine headache is associated with changes in 5-hydroxytryptamine (5HT) metabolism. Thus Sicuteri, Testi, and Anselmi (1961) reported grossly elevated urinary excretion of 5-hydroxyindoleacetic acid (5HIAA), the main urinary metabolite of 5HT, by migrainous subjects on days when attacks occurred. Increased excretion was also found by Curran, Hinterberger, and Lance (1965), although not at such a high level as reported by Sicuteri et al. (1961) while Curzon, Theaker, and Phillips (1966) found a correlation between high 5HIAA excretion and migraine attacks but in only two out of nine subjects studied. Increased urinary 5HLAA is probably due to breakdown of abnormally large amounts of 5HT released from sites in intestine, brain, blood platelets, etc., where it is unavailable to the enzyme monoamine oxidase required for its conversion to 5HIAA. A fall in plasma 5HT has been reported during migraine attacks (Curran et al., 1965; Anthony, Hinterberger, and Lance, 1967). The mechanism by which this occurs may be similar to that by which reserpine causes release of 5HT from platelets (Hinterberger, Anthony, and Vagholkar, 1968). It is also known that reserpine may precipitate migraine attacks (Kimball and Friedman, 1961). Spontaneous migraine is not easy to study biochemically, as the frequency of attacks is of only limited predictability and may decrease when patients are hospitalized and subjected to the attention necessary for biochemical investigation. It has been suggested, therefore, that reserpine induced attacks could be more conveniently studied than spontaneous attacks (Curzon, 1967). The relevance of such study to spontaneous migraine is dependent upon the degree of similarity of the reserpine headache symptoms and of the associated biochemical changes to those occurring in spontaneous migraine. Therefore, the relationship of reserpine induced migraine to urine 5HIAA and blood 5HT changes was studied. High urinary excretion of 3-methoxy4-hydroxy mandelic acid (VMA) a terminal metabolite of noradrenaline and adrenaline, has been reported in spontaneous migraine by some investigators (Sicuteri, 1963; Curran et al., 1965) but has not been found by others (Curzon et al., 1966). The relationship of urinary VMA changes after reserpine headache was therefore also investigated.