oxymorphone and methylnaltrexone

Topics: Doping in Sports; Drug Stability; Gas Chromatography-Mass Spectrometry; Humans; Naltrexone; Narcotic Antagonists; Narcotics; Oxymorphone; Quaternary Ammonium Compounds; Substance Abuse Detection

Topics: Animals; Ethers; In Vitro Techniques; Methylation; Naloxone; Naltrexone; Narcotic Antagonists; Oxymorphone; Quaternary Ammonium Compounds; Receptors, Opioid; Structure-Activity Relationship

Naloxone and naltrexone were compared with their quaternary analogues naloxone methobromide and naltrexone methobromide for efficacy in suppressing intracranial self-stimulation behavior. These quaternary analogues effectively block opiate receptors in the periphery, but since they do not readily cross the blood-brain barrier they have little effect on central receptors. Rats with electrodes in the nucleus accumbens were trained to self-stimulate in daily 60-min sessions. Naloxone (0.2, 2.0 and 20 mg/kg) and naltrexone (20 mg/kg) potently suppressed self-stimulation behavior. In contrast, neither naloxone methobromide (0.2 and 20 mg/kg) nor naltrexone methobromide (20mg/kg) had any significant effects on this behavior. These results suggest that blockade of peripheral opiate receptors alone is insufficient to suppress self-stimulation, and therefore support the idea that opiate antagonists suppress self-stimulation by blockade of central receptors that mediate reinforcement.

Topics: Animals; Brain Mapping; Male; Motivation; Naloxone; Naltrexone; Narcotic Antagonists; Nucleus Accumbens; Oxymorphone; Quaternary Ammonium Compounds; Rats; Rats, Inbred Strains; Receptors, Opioid; Self Stimulation; Septal Nuclei