Abstract
Dimeric opioid analogues linked to a pyrazinone platform, 3-[Tyr/Dmt-NH(CH2)m]-6-[Tyr/Dmt-NH(CH2)n]-2(1H)-pyrazinone (m, n=3 or 4), were synthesized. The Tyr-containing compound (m=4, n=3) exhibited mu-receptor affinity (K(i)mu; 7.58 nM) comparable to that of morphine, while the Dmt derivatives exhibited considerably higher affinity (K(i)mu; 0.021-0.051 nM) with corresponding agonism (IC50=1.79-4.93 nM). Interestingly one compound (m=4, n=3) revealed modest delta-opioid agonism; the converse analogue (m=3, n=4), however, was inactive in MVD assay.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding, Competitive
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Models, Chemical
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Narcotic Antagonists* / chemical synthesis*
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Narcotic Antagonists* / pharmacology
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Pyrazines / chemical synthesis*
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Pyrazines / pharmacology
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Rats
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, mu / antagonists & inhibitors
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Tyrosine / analogs & derivatives*
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Tyrosine / chemical synthesis
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Tyrosine / pharmacology
Substances
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Narcotic Antagonists
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Pyrazines
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Receptors, Opioid, delta
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Receptors, Opioid, mu
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Tyrosine