Abstract
The potent delta-opioid receptor antagonist H-2',6-L-tyrosine(Dmt)-1, 2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic-OH) exhibited partial inverse agonism (EC(50)=6.35 nM, E(max)=-18.87%) for [35S]GTPgammaS binding and H-Dmt-Tic-NH(2) was a neutral antagonist (no effect up to 30 microM). In contrast N,N(CH(3))(2)-Dmt-Tic-NH(2) was a full inverse agonist (EC(50)=2.66 nM, E(max)=-35.95%) similar to ICI 174864 ([N,N-diallyl-Tyr(1),Aib(2,3),Leu(5)]enkephaline) but with a 3.5-fold higher EC(50). In comparison, naltrindole was a neutral antagonist while its analogue HS 378 was a partial inverse agonist (E(max)=-12.99%).
MeSH terms
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Benzamides / pharmacology
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Benzeneacetamides*
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Binding, Competitive / drug effects
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Cell Line
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Dipeptides / chemistry
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Dipeptides / pharmacology*
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Dose-Response Relationship, Drug
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
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Humans
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Isoquinolines / chemistry
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Isoquinolines / pharmacology*
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Naltrexone / analogs & derivatives*
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Naltrexone / chemistry
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Naltrexone / pharmacology*
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Narcotic Antagonists / pharmacology*
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Piperazines / pharmacology
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Pyrrolidines / pharmacology
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Receptors, Opioid, delta / agonists*
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Receptors, Opioid, delta / antagonists & inhibitors
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Receptors, Opioid, kappa / agonists
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Receptors, Opioid, mu / agonists
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Sulfur Radioisotopes
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Tetrahydroisoquinolines*
Substances
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Benzamides
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Benzeneacetamides
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Dipeptides
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Isoquinolines
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Narcotic Antagonists
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Piperazines
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Pyrrolidines
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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Sulfur Radioisotopes
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Tetrahydroisoquinolines
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tyrosyl-1,2,3,4-tetrahydro-3--isoquinoline-carbonyl-alanine
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
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Guanosine 5'-O-(3-Thiotriphosphate)
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Naltrexone
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naltrindole
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U 69593