Vascular Effects of Dihydrogenated Ergot Alkaloids

Abstract

Mellander & Nordenfeldt' have shown by means of a water-filled plethysmograph that following the intravenous injection of dihydroergotamine (DHE) into normal subjects, there is vasoconstriction of the capacitance vessels in the lower limbs. At the same time they showed that the arterial resting flow was almost unaffected. The conclusion of their investigation was that DHE can be used in vasomotor disturbances of the capacitance vessels.In the present investigation, an air-filled rubber cuff plethysmograph was used to compare the effect of DHE and a new synthetic hydrogenated ergot alkaloid, dihydroergostine (DE 145-Sandoz), on the capacitance vessels and the resting blood flow in the lower extremities. Chemistry and pharmacology of dihydroergostine As seen in fig. 1, the chemical structure of DE 145 and DHE has the following components in common: DH-lysergic acid, L-Proline and L-Phenylalanine. The two compounds differ with respect to the composition of the «-hydroxyamino acid which binds the peptide half to the DH-lysergic acid. In the case of DE 145, the acid is a-hydroxy-a-aminobutyric acid, and in DHE this part of the alkaloid molecule consists of «-hydroxyalanine.Pharmacologically, there is also a certain resemblance between the two alkaloids. Both substances inhibit spontaneous or ergometrine-induced contractions of the rabbit uterus2. In spinal cats, a rise in blood pressure is seen after the intravenous administration of 10-50 tLg/kg, and both compounds produce a prolonged increase in tone in segments of freshly excised femoral vein from dogs. The «-adrenolytic effect of DE 145 is greater than that of DHE.2 2 The re-uptake of neuronally-released noradrenaline within the amine depots of the nerve endings is inhibited by both DE 145 and DHE. 2, 3 METHODThe investigation was carried out by means of an air-filled rubber cuff plethysmograph applied to the thickest part of the calf. The arterial resting flow was recorded during venous stasis, produced by means of a cuff placed just proximally to the patella.4 The changes in volume following medication, at UNIV OF MASSACHUSETTS on April 9, 2015 ang.sagepub.com Downloaded from

Maximum oxygen consumption rate and dihydrogenated ergot alkaloids in humans.

“…The pharmacological effects of these drugs on resting subjects have been investigated in numerous studies (Mellander and Nordenfelt, 1970;Ulrich and Siggaard-Andersen, 1971), whereas investigations performed during muscular work are few. The purpose of the present study was to investigate the influence of an ergot alkaloid (dihydro-ergostine) upon the maximal oxygen uptake (V02 max) and to follow some metabolic and circulatory variables during graded bicycle exercise in young sedentary men.…”

“…At the start of the test situation either dihydroergostine (Ulrich and Siggaard-Andersen, 1971) 2 mg or placebo (0.9 per cent saline) were given intravenously in the arm. The two preparations were given in a randomised sequence, and neither the investigators nor the subjects did know which of the two preparations was given.…”