Studies of the effect of natural and synthetic polypeptide type ergot compounds on a peripheral vascular bed

Abstract

1 Six ergot alkaloids were tested for their effect on vascular resistance and for α-adrenergic blocking activity on the innervated perfused hind limb of the dog. The results were compared with those obtained earlier for three compounds of the ergotamine group. 2 Ergostine, dihydroergostine, 1-methylergostine and dihydroergocristine resembled ergotamine, dihydroergotamine and 1-methylergotamine in eliciting vasoconstriction at low vascular resistance and vasodilatation at high vascular resistance. The changeover occurred at the following “inversion points”: ergostine and dihydroergostine as with ergotamine and dihydroergotamine at about 4 R.U.; 1-methylergostine as with 1-methylergotamine at about 2·3 R.U.; dihydroergocristine at about 1·9 R.U. [1 R.U. = 1 resistance unit = 1 mm Hg/ml. per min.] 3 1-methyldihydroergocristine consistently elicited vasodilatation (for initial vascular resistances down to 1·3 R.U.) and 5′-methylergoalanine always caused vasoconstriction (for initial values up to 5·8 R.U.). 4 Ergostine and 5′-methylergoalanine had the most powerful vasoconstrictor effect, which was of the same order of magnitude as that of ergotamine. Dihydroergostine, like dihydroergotamine, was considerably less active. Both 1-methylergostine and 1-methylergotamine elicited only weak vasoconstriction. Moreover, when the initial vascular resistance exceeded the critical inversion value, they elicited only weak vasodilatation. Dihydroergocristine and 1-methyldihydroergocristine had the least effect on vascular resistance. 5 The increase in vascular resistance by noradrenaline was inhibited in a dose-dependent manner by all the ergot alkaloids investigated. Ergostine, 5′-methylergoalanine and ergotamine had the greatest α-adrenergic blocking activity and 1-methylergostine, 1-methyldihydroergocristine and 1-methylergotamine the weakest. The activity of dihydroergostine, dihydroergocristine and dihydroergotamine fell between these two extremes. 6 No correlation was found between the qualitative effect of these ergot alkaloids on vascular resistance (inversion point) and (a) their quantitative effect on this parameter or (b) their α-adrenergic blocking activity. Determination of the inversion point thus provides additional pharmacological information on the vasoactive properties of the ergot alkaloids.