Abstract
N(1)-Alkylation of 1H-benzimidizole of the delta agonist H-Dmt-Tic-NH-CH(2)-Bid with hydrophobic, aromatic, olefinic, acid, ethyl ester, or amide (1-6) became delta antagonists (pA(2)=8.52-10.14). delta- and micro-Opioid receptor affinities were high (K(i)delta=0.12-0.36 nM and K(i)micro=0.44-1.42 nM). Only delta antagonism (pA(2)=8.52-10.14) was observed; micro agonism (IC(50)=30-450 nM) was not correlated with changes in alkylating agent or delta antagonism, and some compounds yielded mixed delta antagonism/micro agonism.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkylation
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Animals
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Benzimidazoles / chemistry*
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Benzimidazoles / pharmacology
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Dipeptides / chemistry*
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Dipeptides / pharmacology
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Guinea Pigs
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Ileum / drug effects
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Inhibitory Concentration 50
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Male
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Mice
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Rats
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Receptors, Opioid, delta / agonists*
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Receptors, Opioid, delta / antagonists & inhibitors*
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Synaptosomes / drug effects
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Vas Deferens / drug effects
Substances
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2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 1H-benzimidazol-2-ylmethylamide
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Benzimidazoles
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Dipeptides
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Receptors, Opioid, delta
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benzimidazole