Modification of vascular response to serotonin by drugs.

ER~TONIN S (s-hydroxytryptamine) has only Bouckaert and Moraes (8) to reverse the vasorecently been isolated, synthesized and constrictor activity of defibrinated blood in available in quantities sufficient to study perfusion experiments; its action against pure its pharmacologic actions. In a brief span of serotonin is evaluated here; e) Pitressin tends time several publications have appeared sugto oppose adrenergic blockade as Grimson (9) gesting that it may be important in normal and we (IO) have observed; its action against physiology. In addition to a direct vasoconthe serotonin-blocking action of ergotamine strictor action, a ganglion-blocking action, is studied here; f) I-hydrazino-phthalazine diminishes the pressor and increases the depressor action of serotonin (I, I I) ; this effect is examined further; g) because of a structural similarity to serotonin, calycanthine, sempervirine, quinamine, serpentine and lysergic acid were studied. and one initiating a von Bezold-like effect, serotonin has a strong peripheral inhibitory effect on neurogenic vasoconstriction (I, 2). Serotonin also inhibits tonic contraction in invertebrate smooth muscle (3), and demonstration of its presence there has prompted the suggestion that it may occur as a normal relaxing agent. It appears in blood with clotting (4) and it has been found in mammalian spleen and intestinal mucosa (enteramine) (5, 6); work now in progress in this laboratory strongly suggests its presence in other mammalian tissues. As evidence accumulates that may establish serotonin an important place in vascular homeostasis, study of the modifying effects of other drugs on vascular response to serotonin becomes cogent. Drugs to be examined are: a) the antimetabolites, z-methyl-3-ethyls-aminoindole and 2-methyl-3-ethyl-s-nitroindole, which have been shown by Woolley and Shaw (7) to oppose the pressor action of serotonin. We wished to confirm and extend their observations and compare these drugs with other blocking agents; b) the antihistamine drugs were used to determine whether the hypotensive action of serotonin in cats and neurogenic hypertensive dogs (I) might be due, in part, to release of histamine; c) because of structural similarities between some of the adrenergic-blocking agents and serotonin, the effectiveness of several is compared with that of other serotonin-blocking agents; d) ergotamine has been shown by Heymans,