nalbuphine and Morphine-Dependence

Topics: Analysis of Variance; Codeine; Cyclazocine; Dextropropoxyphene; Dose-Response Relationship, Drug; Emotions; Humans; Levallorphan; Lysergic Acid Diethylamide; Morphine Dependence; Nalbuphine; Nalorphine; Narcotic Antagonists; Pentazocine; Placebos; Substance Withdrawal Syndrome; Surveys and Questionnaires

In opioid-dependent subjects, the low-efficacy mu agonist nalbuphine generally precipitates withdrawal or withdrawal-like stimulus effects. To provide a more complete characterization of the discriminative stimulus effects of nalbuphine in opioid-treated subjects, seven White Carneux pigeons were treated daily with 10 mg/kg morphine i.m. and trained 6 h later to discriminate among 10 mg/kg morphine, 1.0 mg/kg nalbuphine, and saline by responding on one of three different keys. When tested, morphine produced morphine-key responding and nalbuphine produced nalbuphine-key responding. Replacing the daily morphine injection with saline produced nalbuphine-key responding, and this effect was reversed by the administration of morphine. In substitution tests with other compounds, the antagonists naltrexone (i.m.) and CTAP (D-Phe-Cys-Tyr-D-Tryp-Lys-Thr-Pen-Thr-NH2) (i.c.v.) produced nalbuphine-key responding. High-efficacy agonists fentanyl and etorphine produced morphine-key responding. The intermediate-efficacy agonists buprenorphine, dezocine, and butorphanol produced a pattern of morphine-, saline-, and/or nalbuphine-key responding that differed across individual pigeons. The lower efficacy agonists nalorphine and levallorphan produced predominantly nalbuphine-key responding. The kappa agonists spiradoline and U50,488 [trans-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide methanesulfonate], the nonopioid d-amphetamine, and saline produced predominantly saline-key responding. Naltrexone and nalbuphine dose dependently reversed the morphine-key responding produced by the training dose of morphine. Together, these data suggest that the discriminative-stimulus effects of the low-efficacy micro agonist nalbuphine in morphine-treated pigeons are similar to those of other low-efficacy agonists, naltrexone, and the termination of daily morphine treatment.

Topics: Animals; Columbidae; Conditioning, Operant; Discrimination Learning; Disease Models, Animal; Morphine; Morphine Dependence; Nalbuphine; Narcotics; Sodium Chloride

Topics: Animals; Butorphanol; Drug Synergism; Mice; Morphinans; Morphine Dependence; Motor Activity; Nalbuphine; Pentazocine; Tripelennamine

The mixed agonist-antagonist analgesics buprenorphine, butorphanol, nalbuphine, pentazocine and picenadol were compared to the prototype mu and kappa agonists morphine and Mr 2033, respectively, in the following tests in rhesus monkeys: overt behavioral effects upon acute administration in drug-naive animals; discriminative stimulus properties in monkeys trained to respond to either etorphine or ethylketazocine; self-administration of the test agent relative to codeine; single dose suppression and precipitation in withdrawn and non-withdrawn morphine-dependent monkeys, respectively; and primary addiction studies in drug-naive animals. Whereas both buprenorphine and nalbuphine precipitate withdrawal in morphine-dependent monkeys, withdrawal following chronic administration of buprenorphine resulted in no observable signs of abstinence, while nalbuphine withdrawal was similar to that seen in morphine-dependent monkeys. Butorphanol, pentazocine and picenadol all produced mild dependence of the kappa-type; that is, natural withdrawal behavior similar to that seen following chronic Mr 2033 administration.

Topics: Animals; Behavior, Animal; Benzomorphans; Buprenorphine; Butorphanol; Codeine; Discrimination, Psychological; Humans; Macaca mulatta; Morphinans; Morphine; Morphine Dependence; Nalbuphine; Narcotic Antagonists; Pentazocine; Piperidines; Substance Withdrawal Syndrome

The ability of four opiate partial agonists (buprenorphine, xorphanol, nalbuphine and butorphanol) to produce antinociception and morphine-like physical dependence was examined in the rat. For comparative purposes, morphine was also tested. Dose-response curves were constructed using the rat tail pressure test for analgesia which indicated a rank order of potency of buprenorphine much greater than morphine greater than butorphanol greater than xorphanol = nalbuphine. Assessment of primary physical dependence liability was made using the technique of chronic intraperitoneal infusion followed by precipitation of abstinence with the opiate antagonist, naloxone. The results clearly indicate that buprenorphine was not only the most potent antinociceptive agent, but also possessed the lowest incidence of physical dependence as indicated by precipitated abstinence signs. The other opiates were very much weaker as antinociceptive agents and all produced clear signs of physical dependence.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Butorphanol; Humans; Male; Morphinans; Morphine; Morphine Dependence; Nalbuphine; Nociceptors; Rats; Rats, Inbred Strains

The purpose of the study was to define possible self-administration of nalbuphine, butorphanol and pentazocine by morphine post-addict rats. Rats were prepared with permanent EEG and EMG electrodes and indwelling IV cannulae, made tolerant to and physically dependent on morphine, then trained to lever press for morphine IV self-injections on a fixed ratio (FR) 20 schedule of reinforcement. Rats were then spontaneously withdrawn from morphine. When these morphine post-addict rats were returned to the experimental cages three to four weeks later, they were found to reestablish self-administration of morphine as well as to establish self-administration of nalbuphine, butorphanol and pentazocine. Suppression of REM sleep for at least 30 min was apparent following self-injections of these agents. After the stabilization of self-injection patterns, withdrawal from nalbuphine and pentazocine was found to be associated with intense abstinence symptoms. However, withdrawal from morphine and butorphanol was not. It can be concluded that while drug-seeking behavior for the above narcotics in morphine post-addict rats was analogous as measured by self-administration, nalbuphine and butorphanol appeared to produce lower levels of physical dependence.

Topics: Animals; Butorphanol; Female; Humans; Morphinans; Morphine; Morphine Dependence; Nalbuphine; Pentazocine; Rats; Rats, Inbred Strains; Self Administration; Sleep, REM; Substance Withdrawal Syndrome