Synthesis and Pharmacologic Characterization of an Alkylating Analog (Chlornaltrexamine), of Naltrexone with Ultralong-Lasting Narcotic Antagonist Properties

Philip S Portoghese; D. L. Larson; J. B. Jiang; T. P. Caruso; A. E. Takemori

doi:10.1021/jm00188a008

Synthesis and Pharmacologic Characterization of an Alkylating Analog (Chlornaltrexamine), of Naltrexone with Ultralong-Lasting Narcotic Antagonist Properties

Philip S Portoghese, D. L. Larson, J. B. Jiang, T. P. Caruso, A. E. Takemori

Medicinal Chemistry

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Abstract

Chlornaltrexamine (CNA) produces ultralong-lasting (3-6 days) narcotic antagonism in mice and persistent stereospecific binding to rat-brain homogenate. Protection studies in mice suggest that CNA mediates its narcotic antagonist effects by interacting with the same receptors that are occupied by naloxone. A single icv dose of CNA also has been found to inhibit the development of physical dependence in mice for at least 3 days. These studies suggest that CNA exerts its sustained effects by selective covalent association with opioid receptors.

Original language	English (US)
Pages (from-to)	168-173
Number of pages	6
Journal	Journal of medicinal chemistry
Volume	22
Issue number	2
DOIs	https://doi.org/10.1021/jm00188a008
State	Published - Feb 1 1979

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abstract = "Chlornaltrexamine (CNA) produces ultralong-lasting (3-6 days) narcotic antagonism in mice and persistent stereospecific binding to rat-brain homogenate. Protection studies in mice suggest that CNA mediates its narcotic antagonist effects by interacting with the same receptors that are occupied by naloxone. A single icv dose of CNA also has been found to inhibit the development of physical dependence in mice for at least 3 days. These studies suggest that CNA exerts its sustained effects by selective covalent association with opioid receptors.",

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AU - Jiang, J. B.

AU - Caruso, T. P.

AU - Takemori, A. E.

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N2 - Chlornaltrexamine (CNA) produces ultralong-lasting (3-6 days) narcotic antagonism in mice and persistent stereospecific binding to rat-brain homogenate. Protection studies in mice suggest that CNA mediates its narcotic antagonist effects by interacting with the same receptors that are occupied by naloxone. A single icv dose of CNA also has been found to inhibit the development of physical dependence in mice for at least 3 days. These studies suggest that CNA exerts its sustained effects by selective covalent association with opioid receptors.

AB - Chlornaltrexamine (CNA) produces ultralong-lasting (3-6 days) narcotic antagonism in mice and persistent stereospecific binding to rat-brain homogenate. Protection studies in mice suggest that CNA mediates its narcotic antagonist effects by interacting with the same receptors that are occupied by naloxone. A single icv dose of CNA also has been found to inhibit the development of physical dependence in mice for at least 3 days. These studies suggest that CNA exerts its sustained effects by selective covalent association with opioid receptors.

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Synthesis and Pharmacologic Characterization of an Alkylating Analog (Chlornaltrexamine), of Naltrexone with Ultralong-Lasting Narcotic Antagonist Properties

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