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Venoconstrictor responses to ergosine and ergosinine: Evidence for the isomerization of ergosinine
Author(s) -
MüllerSchweinitzer Else,
Ellis Philip,
Ziegler René
Publication year - 1992
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430250207
Subject(s) - in vivo , yohimbine , receptor , in vitro , chemistry , incubation , pharmacology , potency , norepinephrine , antagonism , isomerization , antagonist , medicine , endocrinology , biology , biochemistry , microbiology and biotechnology , dopamine , catalysis
Ergosine and its D‐isolysergic acid derivative ergosinine were investigated on canine saphenous veins both in vivo and in vitro. Following local i.v. infusion in vivo, about 5 times higher doses of ergosinine were necessary to produce the same venoconstrictor response as induced by ergosine. When administered orally, however, both ergot alkaloids were equi‐effective. In vitro methiothepin, a 5‐HT receptor blocker with high affinity for 5‐HT 1 receptors, antagonized venoconstrictor responses to 5‐HT and ergosine within the same concentration range, being significantly less potent when tested against norepinephrine. The reverse was true for the α 2 ‐selective adrenoceptor blocker yohimbine, which was significantly more potent against norepinephrine and ergosine than against 5‐HT, suggesting that ergosine has affinity to both 5‐HT 1 ‐like receptors and α 2 ‐adrenoceptors. Concentration‐response curves to norepinephrine were shifted to the right in a parallel fashion when ergosine or ergosinine were present in the organ baths, suggesting competitive antagonism. The blocking potency of ergosinine increased with increasing incubation times in Krebs‐Henseleit solution becoming similar to that of ergosine when an incubation time of 2 hr was applied. It is suggested that the pharmacological activity of ergosinine is the consequence of an isomerization into its natural stereoisomer ergosine, which may occur both in vivo and in vitro.