Activity of N-Methyl-a- and -β-funaltrexamine at Opioid Receptors

M. S. Mohamed; D. L. Larson; P. S. Portoghese; A. E. Takemori

doi:10.1021/jm00158a043

Activity of N-Methyl-a- and -β-funaltrexamine at Opioid Receptors

M. S. Mohamed, D. L. Larson, P. S. Portoghese, A. E. Takemori

Medicinal Chemistry

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Abstract

The N-methyl analogues (2a, 2b) of the nonequilibrium μ opioid receptor antagonist β-funaltrexamine (lb) were synthesized and evaluated in the guinea pig ileum preparation (GPI). These analogues are highly potent, reversible opioid agonists and possess no nonequilibrium antagonist activity. The ineffectiveness of 2b in protecting against irreversible blockage of μopioid receptors by lb and the fivefold lower reactivity of 2b with cysteine suggest that N-methyl substitution adversely affects both the first and second recognition steps that are essential for effective covalent blockage of opioid receptors.

Original language	English (US)
Pages (from-to)	1551-1553
Number of pages	3
Journal	Journal of medicinal chemistry
Volume	29
Issue number	8
DOIs	https://doi.org/10.1021/jm00158a043
State	Published - 1986

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title = "Activity of N-Methyl-a- and -β-funaltrexamine at Opioid Receptors",

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AU - Takemori, A. E.

PY - 1986

Y1 - 1986

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AB - The N-methyl analogues (2a, 2b) of the nonequilibrium μ opioid receptor antagonist β-funaltrexamine (lb) were synthesized and evaluated in the guinea pig ileum preparation (GPI). These analogues are highly potent, reversible opioid agonists and possess no nonequilibrium antagonist activity. The ineffectiveness of 2b in protecting against irreversible blockage of μopioid receptors by lb and the fivefold lower reactivity of 2b with cysteine suggest that N-methyl substitution adversely affects both the first and second recognition steps that are essential for effective covalent blockage of opioid receptors.

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Activity of N-Methyl-a- and -β-funaltrexamine at Opioid Receptors

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