nalbuphine and Substance-Related-Disorders

Nalbuphine is a potent analgesic with a low side effect and dependence profile in animals and man. Nalbuphine is distinguished from other agonist/antagonist analgesics in having greater antagonist activity and fewer behavioral effects at analgesic doses than pentazocine, butorphanol or buprenorphine. At equi-analgesic doses, nalbuphine is quantitatively similar to nalorphine in regard to its large ratio of antagonist to analgetic activity. Clinical studies have confirmed this balance of strong antagonist to analgesic activity. Nalbuphine has been shown to effectively antagonize the respiratory depressant activity of narcotic analgesics while concomitantly adding to their analgetic responses. Unlike nalorphine or pentazocine, nalbuphine produces few overt behavioral or autonomic effects in animals at doses over 300 times its analgesic range. These findings are confirmed by clinical results which show that nalbuphine produces few psychotomimetic effects, even at elevated dose levels, in contrast to nalorphine or pentazocine. Nalbuphine produces limited respiratory depression in animals and in man. Significant cardiovascular effects have not been found. Nalbuphine was found to produce significantly less inhibition of gastrointestinal activity than any of the clinically useful narcotic or agonist/antagonist analgesics tested in animals. Nalbuphine's analgetic effects are reversed by naloxone doses similar to those which reverse nalorphine's agonist effects. Results in this and other tests suggest that nalbuphine is primarily a kappa-agonist/mu-antagonist analgesic. Unlike pentazocine or buprenorphine, nalbuphine does not suppress the narcotic abstinence syndrome in partly-withdrawn morphine-dependent animals or man. Rather, due to nalbuphine's strong antagonist activity, analgesic-range doses of nalbuphine severely exacerbate the withdrawal syndrome in partly-withdrawn mice, monkeys and humans. Nalbuphine also precipitates a strong abstinence response in non-withdrawn morphine-dependent animals and man. In post-addict humans, analgesic-range doses of nalbuphine are perceived as minimally morphine-like, but higher doses are judged to be progressively more nalorphine-like (i.e. dysphoric), which further limits nalbuphine's abuse potential in drug-seeking individuals. Primary dependence studies have demonstrated that physical dependence is possible at high dose levels that produce marked side effects. Other studies show that dependence is unlikely to be of signi

Topics: Analgesics; Animals; Chemical Phenomena; Chemistry; Depression, Chemical; Discrimination, Psychological; Dogs; Guinea Pigs; Haplorhini; Humans; Mice; Morphinans; Morphine; Nalbuphine; Naloxone; Rabbits; Rats; Receptors, Opioid; Receptors, Opioid, kappa; Receptors, Opioid, mu; Respiration; Self Administration; Sleep Stages; Substance Withdrawal Syndrome; Substance-Related Disorders

Nalbuphine is an agonist/antagonist analgesic. After parenteral administration of 'usual' doses it is approximately equipotent in analgesic activity to morphine on a weight basis. In studies in patients with moderate to severe pain, usually following surgery, the characteristics of analgesia with nalbuphine were comparable to those seen with equianalgesic doses of morphine or pentazocine. It also appears to produce satisfactory anaesthesia when used as a component of a 'balanced' anaesthesia technique, although a relatively low 'ceiling' effect for reduction of anaesthetic requirements with nalbuphine may limit its usefulness in this regard. As with other agonist/antagonist analgesics, a 'ceiling' effect to nalbuphine-induced respiratory depression is also seen, beyond which further depression does not readily occur. However, with usual analgesic doses, respiratory depression seen with nalbuphine is comparable to that with morphine. Important haemodynamic changes have not occurred after usual doses of nalbuphine, even in patients with cardiac disease. Like other agonist/antagonist analgesic drugs, the abuse potential of nalbuphine seems relatively low, but only wider clinical use for longer periods can establish this with certainty. Thus, nalbuphine appears to offer a useful alternative to morphine in patients with moderate to severe pain.

Topics: Administration, Oral; Analgesics, Opioid; Anesthesia; Animals; Hemodynamics; Humans; Kinetics; Morphinans; Nalbuphine; Narcotic Antagonists; Respiration; Substance-Related Disorders

The chemical properties, animal and human pharmacology, analgesic efficacy, relative potency, administration, and adverse effects of nalbuphine, a recently marketed, parenteral, strong analgesic with narcotic antagonist properties, are reviewed. Acute, subacute, and chronic toxicity studies in animals revealed no unusual adverse effects. The abuse potential of nalbuphine in man is probably similar to pentazocine. Respiratory depression produced by usual therapeutic doses of nalbuphine is equivalent to that of morphine; at higher than usual doses, nalbuphine produces less respiratory depression. Nalbuphine has few effects on cardiovascular hemodynamics in patients without cardiac disease or with stable ischemic disease. In patients with acute myocardial infarction, nalbuphine has an advantage over morphine, pentazocine, and butorphanol of not producing hypotension. Nalbuphine is as effective and has the same potency as morphine as an analgesic, with about the same onset, peak, and duration of action. Sedation is the most common adverse effect and occurs about as often as with other strong analgesics. Nausea and vomiting occur less often. In contrast to pentazocine, the frequency of psychotomimetic reactions apparently is very low. On the basis of presently available evidence, nalbuphine appears to have fewer disadvantages than any other parenteral strong analgesic.

Topics: Analgesics; Animals; Hemodynamics; Humans; Morphinans; Nalbuphine; Respiration; Substance-Related Disorders

Topics: Animals; Benzomorphans; Chemical Phenomena; Chemistry; Cyclazocine; Humans; In Vitro Techniques; Models, Biological; Morphinans; Morphine Derivatives; Nalbuphine; Naloxone; Naltrexone; Narcotic Antagonists; Narcotics; Pentazocine; Receptors, Opioid; Structure-Activity Relationship; Substance-Related Disorders; Thebaine

Drug testing plays an important role in the provision of information to health authorities on trends in drug abuse. In the Republic of Korea, the testing of urine and postmortem specimens has been used as part of a programme to monitor and control the abuse of non-controlled drugs, i.e., substances that were not originally included in the lists of controlled substances in that country. Zipeprol, dextromethorphan, carisoprodol and nalbuphine are examples of such drugs, which are widely used as medicines. Increasing levels of abuse of these drugs, including abuse that resulted in fatalities, were confirmed in the Republic of Korea by the results of drug testing. Based on the accumulated data from postmortem specimens, the health authorities in the Republic of Korea subsequently introduced controls on these drugs. A significant drop in fatalities related to the abuse of these non-controlled drugs underlined the importance of timely action for improving community health. In the context of drug testing, the analysis of non-controlled and new drugs always presents a scientific challenge, because specific analytical methods for testing for those drugs are not available. In the Republic of Korea, as part of the drug abuse warning programme, it was necessary to establish methods for the detection and quantification in biological fluids of all four non-controlled drugs and their metabolites in order to monitor the trends in drug abuse. The present paper puts forward epidemiological and clinical data on abuse and fatalities associated with zipeprol, dextromethorphan, carisoprodol and nalbuphine, as well as details of the analytical methods developed.

Topics: Adolescent; Adult; Autopsy; Body Fluids; Carisoprodol; Child; Cross-Cultural Comparison; Dextromethorphan; Drug and Narcotic Control; Drug Interactions; Drug Overdose; Female; Humans; Illicit Drugs; Korea; Male; Middle Aged; Nalbuphine; Piperazines; Population Surveillance; Prescription Drugs; Substance Abuse Detection; Substance-Related Disorders; Suicide; Young Adult

Nalbuphine hydrochloride, a nonscheduled opioid agonist/antagonist analgesic, is currently approved for the treatment of pain. Recently, nalbuphine dependence was reported in three anabolic steroid users in Britain. To further document this phenomenon, we conducted interviews on eleven subjects who reported nalbuphine use. Eight subjects were clinically dependent on nalbuphine, and seven of the subjects who were asked about tolerance and withdrawal with nalbuphine acknowledged these symptoms. Eight subjects, who had never used drugs intravenously before, reported using nalbuphine by this route. Nalbuphine-related morbidity was extensive and included medical complications and psychiatric symptoms. Nalbuphine users also exhibited a high rate of comorbid Axis I disorders, including other substance misuse. Virtually all subjects described widespread nalbuphine use in the gymnasiums they frequented. These observations, together with the recent increase in nalbuphine-related articles in the lay press, suggest that nalbuphine may represent a new drug of abuse among athletes, especially those using anabolic steroids, and that nalbuphine's scheduling status may need to be re-evaluated.

Topics: Adult; Anabolic Agents; Analgesics, Opioid; Female; Health Status; Humans; Male; Nalbuphine; Psychiatric Status Rating Scales; Sports; Substance-Related Disorders; Suicide, Attempted

Three case reports are presented of nalbuphine hydrochloride dependence meeting DSM IIIR and ICD10 criteria for opioid dependence. Nalbuphine hydrochloride is being obtained from illicit sources and used by those using performance enhancing drugs. In some cases this leads to opioid dependence. There is a potential risks of crossover between the misuse of drugs of performance and the misuse of psychoactive drugs by injection. Further research into the dependence potential of nalbuphine and the extent of the crossover between steroid misuse and other psychoactive drug misuse is required. The legal status of nalbuphine should be reviewed in the light of its availability on the black market.

Topics: Adult; Anabolic Agents; Humans; Male; Nalbuphine; Narcotic Antagonists; Substance-Related Disorders

Myocutaneous sclerosis is a known complication of intramuscular and subcutaneous injection of narcotics. We have described the MRI findings of this entity with superimposed infection in a patient addicted to intramuscular and subcutaneously administered nalbuphine. The clinical and imaging features of this disorder are sufficiently characteristic to allow confident diagnosis. This is the first report of this disorder due to nalbuphine.

Topics: Adult; Humans; Injections, Intramuscular; Injections, Subcutaneous; Magnetic Resonance Imaging; Male; Muscles; Nalbuphine; Sclerosis; Skin; Substance-Related Disorders

This study was designed to determine whether opioid mixed agonist-antagonist analgesics other than buprenorphine also selectively reduce cocaine self-administration by rhesus monkeys. The effects of daily treatment with nalbuphine (0.1 to 3 mg/kg/day) or (0.254 to 7.62 mumol/kg/day), butorphanol (0.01 to 0.3 mg/kg/day) or (0.0209 to 0.628 mumol/kg/day), and saline on cocaine and food self-administration were each studied for 40 sessions over 10 consecutive days. Cocaine (0.05 or 0.10 mg/kg/inj) and food (1-gm banana pellets) self-administration were maintained on a fixed ratio 4 (variable ratio 16:S) schedule of reinforcement. Both nalbuphine and butorphanol reduced cocaine self-administration (p < 0.0001) but this effect was not selective since food self-administration also decreased in a dose-dependent manner (p < 0.0001). Nalbuphine administration (1 to 3 mg/kg/day) decreased cocaine injections to 40% to 60% below baseline (p < 0.01) and food pellets 30% to 68% below baseline (p < 0.01). Lower doses of nalbuphine (0.10 and 0.30 mg/kg) did not change cocaine- or food-maintained responding significantly. All doses of butorphanol (0.01 to 0.3 mg/kg/day) reduced cocaine injections to 16% to 58% below baseline (p < 0.01). Food self-administration decreased to 21% to 70% below baseline (p < 0.01) at butorphanol doses of 0.03 to 0.3 mg/kg/day). These data suggest that these opioid mixed agonist-antagonist analgesics may not be useful as pharmacotherapies for the treatment of cocaine abuse.

Topics: Analysis of Variance; Animals; Butorphanol; Cocaine; Conditioning, Operant; Feeding Behavior; Female; Macaca mulatta; Male; Nalbuphine; Receptors, Opioid; Self Administration; Substance-Related Disorders

To assess the stimulus properties of opioid mixed agonist-antagonist drugs in humans, postaddict volunteers were trained in a three-choice drug discrimination procedure to discriminate among the effects of i.m. given saline (4 ml), hydromorphone (3 mg/70 kg) and pentazocine (45 mg/70 kg). Subjects earned monetary reinforcement by correctly identifying the training drugs by letter code. Other subjective, behavioral and physiological measures were also collected. After training, subjects were tested for their ability to discriminate between the three drugs; generalization curves for the training drugs and three mixed agonist-antagonist test drugs (butorphanol, nalbuphine and buprenorphine) were then determined. In generalization testing both hydromorphone and pentazocine produced dose-related increases in drug-appropriate responses and in characteristic subjective effects measures. Butorphanol produced dose-related increases in identifications as pentazocine and in those subjective effect measures increased by pentazocine. Nalbuphine was not consistently identified as either pentazocine or hydromorphone and produced relatively flat dose-response functions on most of the subjective effect measures. At the three highest doses tested buprenorphine was identified in 50% of trials as hydromorphone and in 50% of trials as pentazocine in the discrimination measures and increased subjective effect scales which were characteristic of both hydromorphone and pentazocine. The results are most consistent with butorphanol having the stimulus properties of a kappa agonist and both nalbuphine and buprenorphine having the stimulus properties of partial mu agonists although the profiles of observed drug effects were complicated and not entirely consistent with a simple mu/kappa opioid receptor model.

Topics: Adult; Buprenorphine; Butorphanol; Conditioning, Operant; Discrimination, Psychological; Humans; Hydromorphone; Male; Nalbuphine; Pentazocine; Pupil; Substance-Related Disorders

Topics: Back Pain; Humans; Injections; Morphinans; Nalbuphine; Substance-Related Disorders

Reinforcing thresholds for rewarding brain stimulation to the medial forebrain bundle-lateral hypothalamus were determined in rats by means of a rate-free psychophysical method. Nalbuphine, a mixed agonist-antagonist opioid, alone caused a significant, but modest, dose-dependent lowering of the threshold for reinforcing stimulation. Concomitant administration of an ineffective dose of tripelennamine, an antihistamine, with nalbuphine potentiated the threshold lowering effect of nalbuphine. These results are similar to previous results obtained with tripelennamine and pentazocine suggesting that nalbuphine may have abuse potential if combined with tripelennamine.

Topics: Animals; Drug Interactions; Male; Morphinans; Nalbuphine; Rats; Reinforcement, Psychology; Reward; Self Stimulation; Substance-Related Disorders; Tripelennamine

The agonist/antagonist analgesics, butorphanol (Stadol) and nalbuphine (Nubain), are being increasingly employed as intravenous sedation agents; nalbuphine will be available in the future as an oral analgesic. The drugs possess numerous pharmacologic similarities and some dissimilarities. Both are equianalgesic (and nalbuphine is equipotent) with morphine parenterally and codeine orally. Their pharmacokinetics are similar; nalbuphine has a longer duration of action. Both may precipitate an abstinence syndrome in narcotic-dependent persons and will probably be associated with low-level drug abuse potential. They are both agonists of the kappa opioid receptor and partial agonists of the mu receptor. Butorphanol is a partial agonist of the sigma receptor responsible for psychotomimetic effects. The incidence of adverse effects is low, sedation being the most common. In cardiac-risk patients, nalbuphine does not increase cardiac work or oxygen requirements; nor do increasing doses of nalbuphine increase the duration of respiratory depression. Both drugs possess plateau respiratory depressant actions.

Topics: Anesthesia, Dental; Butorphanol; Codeine; Drug Interactions; Heart; Humans; Kinetics; Morphinans; Nalbuphine; Preanesthetic Medication; Receptors, Opioid; Respiration; Substance-Related Disorders; Therapeutic Equivalency

Topics: Animals; Brain; Cocaine; Dextroamphetamine; Electric Stimulation; Euphoria; Humans; Models, Neurological; Morphine; Nalbuphine; Neural Pathways; Neurons; Rats; Reward; Self Stimulation; Substance-Related Disorders; Tripelennamine

Topics: Analgesics; Azepines; Buprenorphine; Female; Humans; Male; Meptazinol; Morphinans; Nalbuphine; Pregnancy; Substance-Related Disorders

Topics: Analgesics; Animals; Butorphanol; Female; Humans; Morphinans; Morphine; Nalbuphine; Pentazocine; Rats; Self Administration; Sleep, REM; Substance-Related Disorders