Synthesis and pharmacologic characterization of an alkylating analog chlornaltrexamine, of naltrexone with ultralong-lasting narcotic antagonist properties

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 intracerebrovascular dose of CNA inhibits the development of physical dependence on morphine in mice for at least 3 days. CNA apparently exerts its sustained effects by selective covalent association with opioid receptors.