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Quaternary derivatives of naloxone and naltrexone, methyl naloxonium chloride(ORG 10908) and naltrexone methobromide ( MRZ 2663BR ), respectively, were compared with the parent compounds for their ability to antagonize the reinforcing properties of heroin as measured in an operant, i.v., self-administration paradigm. As expected, lower doses (up to 0.2 mg/kg) of naloxone and naltrexone produced dose-dependent increases in heroin self-administration, but at higher doses (10-30 mg/kg) these drugs produced transient decreases (20-100 min) in self-administration followed by recovery. Naltrexone was approximately 1.5 times more potent than naloxone in increasing heroin self-administration at the lower doses (up to 0.2 mg/kg) and had a slightly longer duration of action. The quaternary derivatives were ineffective as antagonists of heroin self-administration in doses 200 times greater than the effective …