Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties.
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.
D000477:Alkylating Agents / Q000138:chemical synthesis*; D000700:Analgesics; D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D009020:Morphine / Q000037:antagonists & inhibitors; D009021:Morphine Dependence / Q000517:prevention & control; D009270:Naloxone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000138:chemical synthesis*; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D013997:Time Factors
D000477:Alkylating Agents; D000700:Analgesics; D009292:Narcotic Antagonists; D009588:Nitrogen Mustard Compounds; D011957:Receptors, Opioid; D009270:Naloxone; D009271:Naltrexone; C017120:chlornaltrexamine; D009020:Morphine