Talk:Lysergol

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Hht2a and adrenoreceptor affinities :)

https://www.ncbi.nlm.nih.gov/pubmed/8923801

Naturally occurring clavines: antagonism/partial agonism at 5-HT2A receptors and antagonism at alpha 1-adrenoceptors in blood vessels.

Pertz H1.

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Abstract

The interaction of eight typical representatives of naturally occurring clavines (agroclavine, costaclavine, dihydrolysergol-l, elymoclavine, festuclavine, lysergene, lysergol, and pyroclavine) with 5-HT2A receptors and alpha 1-adrenoceptors was studied in rat tail artery and aorta, respectively. Clavines antagonized 5-HT-induced contractions with calculated pKB values (pKP values for partial agonists) of 4.84-7.81 and (R)-phenylephrine-induced contractions with calculated pKB values of 5.34-7.09. Specificity of clavines at 5-HT2A receptors relative to alpha 1-adrenoceptors was rather low. Low affinity for costaclavine at both 5-HT2A receptors (pKP = 4.84 +/- 0.06) and alpha 1-adrenoceptors (pKB = 5.34 +/- 0.05) indicates that the trans-junction of ring C and D of the ergoline pharmacophore is crucial for the binding of ergolines to these sites. Lysergol, lysergene, and costaclavine produced non-parallel displacements of the 5-HT concentration-response curve in the rat tail artery and caused small contractions by themselves. Lysergol contracted the rat tail artery with a pEC50 of 6.36 +/- 0.04 and an intrinsic activity of 0.18 +/- 0.03 with respect to 5-HT. Lysergol-induced contractile responses were surmountably antagonized by ketanserin (10 nM) with a pKB of 9.1 which is consistent with an interaction of lysergol with 5-HT2A receptors. The pKP for the lysergol-5-HT2A receptor complex calculated from concentration-response curves to lysergol was 6.88 +/- 0.07 and did not match the pKP of 7.66 +/- 0.02 calculated from antagonism by lysergol of the contractile response to 5-HT. This suggests that lysergol and 5-HT possibly bind in two slightly different orientations at the 5-HT2A receptor. It is concluded that partial agonism and pure antagonism at 5-HT2A receptors on the one side and antagonism at alpha 1-adrenoceptors on the other side may contribute to the noxious effects of naturally occurring clavines.

PMID: 8923801 DOI: 10.1055/s-2006-957922

[Indexed for MEDLINE]

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MeSH terms, Substances

Iownutopia 11:04, 13 June 2017 (UTC)  — Preceding unsigned comment added by Iownutopia (talk • contribs)

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