nalorphine and Heroin-Dependence

When an opioid capable of forming active metabolites is administered, the total pharmacology is the result of interactions of the opioid and such metabolites, especially normetabolites. Normetabolites may affect the morphine-like characteristics of certain opioids and thus influence their reinforcement in animals and man. Most opioids, when administered in single doses, are positively reinforcing in addicts. Oral administration, as compared with parenteral, facilitates the formation of normetabolites. When chronically administered, many opioids, including acetylmethadol, meperidine, morphine, codeine, propoxyphene, and levorphanol, show evidence of a longer half-life for their normetabolites. Normetabolites may have aversive characteristics and thus impair positive reinforcement of the parent drug in animals and man. For example, addicts do not like chronic oral morphine or chronic oral codeine. Conversely, methadone, the normetabolites of which are inactive, is well accepted during chronic oral administration. Drugs which inhibit N-demethylation will increase the agonist potency of opioids having inactive normetabolites (e.g., methadone) but will decrease the agonist potency of opioids having more potent normetabolites than the parent (e.g., acetylmethadol). The divergent responses of addicts to single doses of opiates as compared with chronic doses indicate that chronic addiction tests in man are needed befored relative abuse liability can be predicted.

Topics: Animals; Dealkylation; Dextropropoxyphene; Dogs; Haplorhini; Heroin Dependence; Humans; Methadone; Methyltransferases; Morphine Dependence; Nalorphine; Narcotics; Pupil; Reinforcement, Psychology; Self Administration; Species Specificity; Time Factors

Topics: Administration, Oral; Apgar Score; Birth Weight; Child; Child Care; Female; Gestational Age; Heroin Dependence; Humans; Infant, Newborn; Levallorphan; Maternal-Fetal Exchange; Methadone; Nalorphine; Naloxone; Phenobarbital; Poisoning; Pregnancy; Substance Withdrawal Syndrome; Tablets

The effects of morphine, naltrexone, and nalorphine were studied in rats trained to lever-press for intravenous heroin and then tested under conditions of non-reinforcement. Animals were reinforced for lever-pressing on a continuous reinforcement schedule (100 micrograms/kg per infusion) for 2-3 h each day following which reinforcement was terminated and animals were studied under extinction conditions for the remainder of the session. Each day following the termination of responding under extinction conditions, animals were given a single injection of saline, morphine, nalorphine, or naltrexone; lever-pressing under the extinction conditions was then observed for several hours. When animals adapted to this regimen, very low levels of responding were seen following saline injections; morphine (2 or 10 mg/kg) reinstated vigorous responding that lasted 1-4 h. Naltrexone (2 mg/kg) suppressed responding below the levels seen after saline, and nalorphine (10 mg/kg) had the same effect as saline. These observations support the view that opioid-seeking behavior is primed by the proponent or opioid-like actions of opioids and not by the opponent or drug-opposite effects associated with opioid withdrawal.

Topics: Animals; Conditioning, Operant; Extinction, Psychological; Heroin Dependence; Injections, Intravenous; Morphine; Nalorphine; Naltrexone; Rats; Rats, Sprague-Dawley; Self Administration

Drugs which specifically antagonize certain of the actions of opioids are reviewed. These antagonists include nalorphine, levallorphan, naloxone, naltrexone, and cyclazocine. Programs involving antagonist treatment are discussed.

Topics: Aftercare; Cyclazocine; Extinction, Psychological; Heroin Dependence; Hospitalization; Humans; Levallorphan; Methadone; Nalorphine; Naloxone; Naltrexone; Narcotic Antagonists; Psychotherapy; Receptors, Opioid

Topics: Emergencies; Heroin; Heroin Dependence; Humans; Nalorphine; Naloxone; Pulmonary Edema; Respiratory Insufficiency; Substance-Related Disorders

Topics: Chromatography, Thin Layer; Evaluation Studies as Topic; Heroin Dependence; Humans; Nalorphine; Prisoners; Pupil; Substance-Related Disorders; Urine

Topics: Drug Tolerance; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Methadone; Nalorphine; Opium; Rehabilitation Centers; Socioenvironmental Therapy; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

Topics: American Medical Association; Analgesics; Animals; Heroin Dependence; Humans; Injections, Intramuscular; Injections, Subcutaneous; Legislation, Drug; Nalorphine; Pentazocine; Substance Withdrawal Syndrome; Substance-Related Disorders; United States; World Health Organization