The irreversible narcotic antagonistic and reversible agonistic properties of the fumaramate methyl ester derivative of naltrexone

A. E. Takemori; Dennis L. Larson; P. S. Portoghese

doi:10.1016/0014-2999(81)90355-1

The irreversible narcotic antagonistic and reversible agonistic properties of the fumaramate methyl ester derivative of naltrexone

A. E. Takemori, Dennis L. Larson, P. S. Portoghese

Medicinal Chemistry

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Abstract

The fumaramate methyl ester derivatives of naltrexone (β-FNA) and oxymorphone (β-FOA) were both found to be reversible agonists on the guinea pig ileal longitudinal muscle preparation. In addition, β-FNA possessed an irreversible antagonistic effect against morphine whereas β-FOA had no such capacity. Analysis by pA₂ values revealed that β-FOa resembled pure agonists like morphine and enkephalin while β-FNA resembled the mixed agonist-antagonists like nalorphine and pentazocine. The antagonism by β-FNA was very selective in that it antagonized pure agonists but had little or no effect on the effects of either mixed agonists, ethylketocyclazocine or other non-opiate-type agonists like norepinephrine.

Original language	English (US)
Pages (from-to)	445-451
Number of pages	7
Journal	European Journal of Pharmacology
Volume	70
Issue number	4
DOIs	https://doi.org/10.1016/0014-2999(81)90355-1
State	Published - Apr 9 1981

Bibliographical note

Funding Information:
* This work was supported by U.S. Public Health Service Grants DA00289 and DA01533 from the National Institute on Drug Abuse. ** To whom correspondence should be addressed: Department of Pharmacology, University of Minnesota, 435 Delaware Street S.E., 3-260 Millard Hall, Minneapolis, Minnesota 55455, U.S.A.

Keywords

Agonist
Antagonist
Fumaramate methyl ester derivative
Guinea pig ileum
Naltrexone
Narcotic
Opioid receptor
Oxymophone

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title = "The irreversible narcotic antagonistic and reversible agonistic properties of the fumaramate methyl ester derivative of naltrexone",

abstract = "The fumaramate methyl ester derivatives of naltrexone (β-FNA) and oxymorphone (β-FOA) were both found to be reversible agonists on the guinea pig ileal longitudinal muscle preparation. In addition, β-FNA possessed an irreversible antagonistic effect against morphine whereas β-FOA had no such capacity. Analysis by pA2 values revealed that β-FOa resembled pure agonists like morphine and enkephalin while β-FNA resembled the mixed agonist-antagonists like nalorphine and pentazocine. The antagonism by β-FNA was very selective in that it antagonized pure agonists but had little or no effect on the effects of either mixed agonists, ethylketocyclazocine or other non-opiate-type agonists like norepinephrine.",

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note = "Funding Information: * This work was supported by U.S. Public Health Service Grants DA00289 and DA01533 from the National Institute on Drug Abuse. ** To whom correspondence should be addressed: Department of Pharmacology, University of Minnesota, 435 Delaware Street S.E., 3-260 Millard Hall, Minneapolis, Minnesota 55455, U.S.A.",

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AU - Portoghese, P. S.

N1 - Funding Information: * This work was supported by U.S. Public Health Service Grants DA00289 and DA01533 from the National Institute on Drug Abuse. ** To whom correspondence should be addressed: Department of Pharmacology, University of Minnesota, 435 Delaware Street S.E., 3-260 Millard Hall, Minneapolis, Minnesota 55455, U.S.A.

PY - 1981/4/9

Y1 - 1981/4/9

N2 - The fumaramate methyl ester derivatives of naltrexone (β-FNA) and oxymorphone (β-FOA) were both found to be reversible agonists on the guinea pig ileal longitudinal muscle preparation. In addition, β-FNA possessed an irreversible antagonistic effect against morphine whereas β-FOA had no such capacity. Analysis by pA2 values revealed that β-FOa resembled pure agonists like morphine and enkephalin while β-FNA resembled the mixed agonist-antagonists like nalorphine and pentazocine. The antagonism by β-FNA was very selective in that it antagonized pure agonists but had little or no effect on the effects of either mixed agonists, ethylketocyclazocine or other non-opiate-type agonists like norepinephrine.

AB - The fumaramate methyl ester derivatives of naltrexone (β-FNA) and oxymorphone (β-FOA) were both found to be reversible agonists on the guinea pig ileal longitudinal muscle preparation. In addition, β-FNA possessed an irreversible antagonistic effect against morphine whereas β-FOA had no such capacity. Analysis by pA2 values revealed that β-FOa resembled pure agonists like morphine and enkephalin while β-FNA resembled the mixed agonist-antagonists like nalorphine and pentazocine. The antagonism by β-FNA was very selective in that it antagonized pure agonists but had little or no effect on the effects of either mixed agonists, ethylketocyclazocine or other non-opiate-type agonists like norepinephrine.

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KW - Antagonist

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KW - Guinea pig ileum

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KW - Narcotic

KW - Opioid receptor

KW - Oxymophone

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The irreversible narcotic antagonistic and reversible agonistic properties of the fumaramate methyl ester derivative of naltrexone

Abstract

Bibliographical note

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