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

1. Six ergot alkaloids were tested for their effect on vascular resistance and for alpha-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 alpha-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 alpha-adrenergic blocking activity. Determination of the inversion point thus provides additional pharmacological information on the vasoactive properties of the ergot alkaloids.

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