Human 5-hydroxytryptamine venomotor receptors

Abstract

The venoconstriction test (VCT) is a method for exploring the monoamine venomotor receptors in man: it is a painless, innocuous technique, able to give the maximum information with the minimum trouble, according to the requirements of the clinical pharmacological tests. The VCT records the local venospasm when very small amounts of 5-HT, noradrenaline or epinephrine are administered through a needle inserted orthodromically into the vein. The VCT is a suitable technique for an acceptable pharmacological evaluation of the vascular reactivity to 5-HT in man. The threshold effect, even if different from subject to subject, is quite constant in the same subject; the threshold doses of 5-HT in the majority of adult men and women, range between 100 and 500 ng. The inhibiting activity of anti-serotonin drugs such as LSD-25, BOL-148, methysergide, nicergoline, BC-105, cyproheptadine, and MY-25 is evaluated in man in quite a satisfying way. An unexpected result was the enhancement of 5-HT and noradrenaline reactivity by treatment with monoamine oxidase inhibitors. Supersensitivity to 5-HT but not to noradrenaline has been observed following administration of parachlorophenylalanine, a specific 5-HT depletor. Skin reaction, capillary permeability, blood pressure and blood flow are used to test the vascular activity of 5-hydroxytryptamine ( Fontanini et al. 1958; Scherbel and Harrison, 1958; Halpern et al. 1960): however, these parameters, when applied in human pharmacology, are quite unsuitable because of technical difficulties, scarce sensitivity and reproductivity. Human veins are very sensitive to the spasmogenic action of 5-HT ( Magalini et al. 1956). However the venous tone is quite difficult to measure because of the influence of the autonomous nervous system and of the humoral agents ( Duggan et al. 1953; Sharpey-Schafer and Ginsburg, 1962; Sharpey-Schafer, 1963). few years ago a technique was arranged to test the sensitivity of the 5-HT venomotor receptors in man ( Sicuteri et al. 1964). This technique (venoconstriction test: VCT) is based upon the high responsiveness to 5-HT of the vein. The method is highly sensitive, being able to detect the activity of fractions of micrograms of 5-HT; it is practically painless and innocuous, in view of the exiguity of the doses; and the results are quite constant and reproductive. VCT has been used successfully to test agonists, antagonists and correlated drugs on the monoamine (5-HT and catecholamines) venomotor receptors: in the present paper we have collected the most significant information on the human pharmacology of the 5-HT venomotor reactivity, reported fragmentarily in short communications ( Sicuteri et al. 1964a; 1965; 1966).