nalorphine and Substance-Related-Disorders

Drug self-administration is controlled, in part, by the subject's history of drug exposure. Although a history of drug administration is not necessary for many drugs to function as reinforcers, prior exposure can increase the likelihood that certain drugs, such as ethanol, will maintain behavior. While it has been demonstrated that physiological dependence is not necessary for a drug to function as a reinforcer, the conditions under which such dependence is maintained can control the later self-administration of the drug. Once drug-maintained behaviors are established, the particular drug that maintains behavior can influence the initial pattern of intake of a new drug and thus the dose of that drug that will maintain behavior. Additionally, under certain conditions, similarity between the discriminative stimulus effects of the drug that previously maintained behavior and those of a new drug can increase the likelihood that the new drug will function as a reinforcer. Finally, stimuli that have been paired with drug administration can powerfully control later drug-maintained behavior, the direction of such control being determined by the conditions under which such pairing occurred. In summary, both the type of drug with which a subject has experience as well as the contingencies governing that experience contribute to subsequent drug self-administration.

Topics: Animals; Behavior, Animal; Dextrorphan; Drug Interactions; Humans; Macaca mulatta; Morphine; Nalorphine; Narcotic Antagonists; Narcotics; Rats; Reinforcement, Psychology; Self Administration; Substance-Related Disorders

Topics: Analgesics; Animals; Behavior, Animal; Dogs; Drug Evaluation, Preclinical; Female; Haplorhini; Humans; Kinetics; Male; Methadone; Methadyl Acetate; Mice; Morphine; Nalorphine; Rabbits; Rats; Stereoisomerism; Substance-Related Disorders; Time Factors

Topics: Analgesics; Animals; Chemical Phenomena; Chemistry; Codeine; Drug Tolerance; Guinea Pigs; Half-Life; Haplorhini; Humans; Ileum; In Vitro Techniques; Meperidine; Mice; Molecular Conformation; Morphinans; Nalorphine; Narcotic Antagonists; Pentazocine; Rats; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders; Tail

Topics: Animals; Chlorpromazine; Codeine; Cyclazocine; Drug Combinations; Drug Evaluation; Drug Evaluation, Preclinical; Humans; Lysergic Acid Diethylamide; Mice; Morphinans; Morphine; Morphine Dependence; Nalorphine; Naloxone; Narcotic Antagonists; Pentobarbital; Rats; Receptors, Drug; Species Specificity; Substance Withdrawal Syndrome; Substance-Related Disorders; Surveys and Questionnaires

Topics: Analgesics; Blood Circulation; Fentanyl; Humans; Intestines; Levallorphan; Meperidine; Methadone; Methotrimeprazine; Morphinans; Morphine; Nalorphine; Narcotic Antagonists; Nausea; Pain; Pentazocine; Psychopharmacology; Respiration; Substance-Related Disorders; Urinary Tract; Vomiting

Topics: Analgesics; Aspirin; Caffeine; Clinical Trials as Topic; Codeine; Dextropropoxyphene; Female; Headache; Humans; Indoles; Isoquinolines; Meperidine; Morphine; Nalorphine; Narcotics; Pain; Periodontal Diseases; Phenacetin; Placebos; Postoperative Care; Pregnancy; Puerperal Disorders; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

This report-the second of a series on codeine and its alternates for pain and cough relief-contains a detailed evaluation of experimental and clinical data on newer substances having analgesic properties comparable to and in approximately the same range as those of codeine. The data are discussed under the headings: analgesic effects in animals; clinical usefulness; side-effects with particular reference to dependence and abuse liability.

Topics: Amides; Analgesics; Animals; Antitussive Agents; Azepines; Carisoprodol; Cats; Chickens; Codeine; Cough; Cyclazocine; Dextropropoxyphene; Diphenylacetic Acids; Dogs; Ducks; Guinea Pigs; Humans; Indenes; Indoles; Isoquinolines; Mice; Morphinans; Nalorphine; Narcotic Antagonists; Pain; Pentazocine; Phenethylamines; Pyrrolidines; Rats; Substance-Related Disorders; Thalidomide

Topics: Adolescent; Amphetamine; Amphetamines; Barbiturates; Cannabis; Codeine; Heroin; Humans; Hydromorphone; Jurisprudence; Meperidine; Mescaline; Methadone; Morphine Dependence; Nalorphine; Narcotic Antagonists; Psychotherapy; Statistics as Topic; Substance-Related Disorders

Topics: Anesthesia; Diagnosis; Fetus; Humans; Infant, Newborn; Nalorphine; Narcotic Antagonists; Pain; Pharmacology; Respiration; Substance-Related Disorders; Toxicology

Topics: Analgesics; Analgesics, Non-Narcotic; Antipyretics; Biomedical Research; Codeine; Cyclazocine; Dextromoramide; Dextropropoxyphene; Heroin; Humans; Hydromorphone; Isonipecotic Acids; Meperidine; Methadone; Methotrimeprazine; Morphine; Nalorphine; Narcotic Antagonists; Oxymorphone; Pentazocine; Phenazocine; Substance-Related Disorders; Toxicology

Topics: Analgesics; Aspirin; Caffeine; Clinical Trials as Topic; Codeine; Dextropropoxyphene; Female; Headache; Humans; Indoles; Isoquinolines; Meperidine; Morphine; Nalorphine; Narcotics; Pain; Periodontal Diseases; Phenacetin; Placebos; Postoperative Care; Pregnancy; Puerperal Disorders; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

Topics: Academies and Institutes; Analgesics; Analysis of Variance; Anxiety; Azocines; Clinical Trials as Topic; Cyclazocine; Emotions; Euphoria; Hearing; Hospitals, Special; Hostility; Humans; Interpersonal Relations; Kentucky; Lysergic Acid Diethylamide; Morphine; Movement; Nalorphine; Narcotic Antagonists; National Institutes of Health (U.S.); Pentobarbital; Perception; Placebos; Problem Solving; Research; Sensation; Substance-Related Disorders; Taste; Time Perception; Touch; United States

Topics: Amphetamine; Analgesics; Barbiturates; Cannabis; Clinical Trials as Topic; Cocaine; Cyclazocine; Drug Tolerance; Euphoria; Humans; Morphine; Nalorphine; Narcotic Antagonists; Pupil; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Analgesics; Clinical Trials as Topic; Drug Tolerance; Humans; Morphine; Nalorphine; Narcotic Antagonists; Placebos; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Animals; Aorta, Thoracic; Cocaine; Cyclic AMP; Electric Stimulation; Guinea Pigs; Humans; Ileum; In Vitro Techniques; Male; Mice; Muscle, Smooth; Opioid-Related Disorders; Rats; Receptors, Dopamine; Receptors, Opioid; Receptors, Serotonin; Substance-Related Disorders

A direct treatment of methanol-washed hair with a silylating solution is proposed to extract heroin, O-6-monoacetylmorphine, morphine, acetylcodeine, and codeine, obtaining the simultaneous derivatization of the hydroxylated metabolites and reducing potential sample contamination. Analysis is performed by capillary gas chromatography-tandem mass spectrometry (GC/MS/MS) using multiple selected reaction monitoring. Owing to the selectivity and sensitivity of the GC/MS/MS analysis, and to the extremely simple treatment of the sample, the method fulfils the requirements of both clinical and forensic diagnosis of heroin use.

Topics: Codeine; Gas Chromatography-Mass Spectrometry; Hair; Heroin; Humans; Illicit Drugs; Morphine; Morphine Derivatives; Nalorphine; Reference Values; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders

The experiments concerned the effects of glucuronate or sulfate conjugation at the 6-position of nalorphine on the analgesic and antagonistic activities and also on the development of tolerance and physical dependence. Nalorphine-3-and 6-sulfate ester were synthesized for the first time. The analgesic effect of nalorphine-6-sulfate and -glucuronide was higher than that of nalorphine when assessed in the acetic acid writhing test. However, these 6-conjugates exhibited less potent agonistic activity in the test with guinea-pig ileum muscle strip and revealed no analgesic effect in the tail pinch test. The antagonistic activity of these 6-conjugates to morphine analgesia was lower on their s.c. injection, but higher on i.c.v. injection than that of nalorphine. The development of tolerance to the analgesia caused by nalorphine was not affected by the 6-modifications. Frequent withdrawal signs were seen in mice treated chronically with anlorphine-6-conjugates by challenging with naloxone while mice treated with nalorphine showed no such signs. This potent enhancing effect of 6-conjugation on the development of physical dependence was suggested to be also the case with morphine. These changes of potency due to conjugation were interpreted as due to the altered interaction with multiple opioid receptors.

Topics: Analgesics; Animals; Biotransformation; Drug Tolerance; Glucuronates; Guinea Pigs; Humans; Ileum; In Vitro Techniques; Male; Mice; Morphine; Muscle Contraction; Muscle, Smooth; Nalorphine; Pentazocine; Structure-Activity Relationship; Substance-Related Disorders; Sulfates

The dependence liability of analgesic and psychotropic drugs as assessed in animal experiments is described. It is demonstrated that the abuse liability of a given drug does not only depend on its pharmacological or psychopharmacological profile of actions. The abuse liability of a drug is, however, greatly influenced by environmental variables, motivation to self-administration of a drug as well as previous drug exposure. Correlations between dependent behavior of animals and dependent behavior of men are discussed.

Topics: Analgesics; Animals; Aspirin; Barbiturates; Conditioning, Operant; Electric Stimulation; Humans; Morphine; Nalorphine; Narcotic Antagonists; Narcotics; Pentazocine; Psychotropic Drugs; Rats; Self Administration; Substance-Related Disorders

1 Physical dependence was produced in ilea from naive guinea-pigs by exposure of the tissue to different opiates for logarithmically-spaced periods of time (20-320 min). The responsiveness of the tissue to naloxone, as indicated by a strong contracture of the ileum, was enhanced in contrast to that found in intestines not exposed to opiates. 2 The dose-response curves to naloxone obtained in tissues individually exposed to different opiates showed that their relative potency in increasing sensitivity to naloxone was as follows: levorphan greater than morphine greater than Met-enkephalin greater than nalorphine greater than pentazocine. 3 The naloxone-induced response was dose-dependent and was directly related to the opiate concentration and length of exposure. 4 Dextrorphan the inactive isomer of levorphan, did not increase the responsiveness of the tissues to the narcotic antagonist, indicating that the phenomenon is stereospecific. 5 The naloxone-induced contraction in ilea exposed for 320 min to morphine (1 x 10(-6)M) was not prevented or suppressed by the administration of a large dose of morphine (1 x 10(-5)M) before or immediately after the naloxone challenge. 6 The evidence presented here shows that a phenomenon resembling in vivo opiate physical dependence can be acutely produced in vitro with pharmacological characteristics similar to other naloxone-induced abstinence effects.

Topics: Animals; Dose-Response Relationship, Drug; Enkephalin, Methionine; Enkephalins; Guinea Pigs; Humans; Ileum; In Vitro Techniques; Levorphanol; Male; Morphine; Nalorphine; Naloxone; Narcotics; Pentazocine; Substance-Related Disorders; Time Factors

A series of 8-alkyl-3-methoxy-17-methylmorphinan-6-ones (3C) and -isomorphinan-6-ones (3T) were prepared by conjugate addition of lithium dialkylcuprates to the corresponding 7,8-didehydro-6-ones 2C and 2T. These 17-methyl compounds were potent analgesics and were converted to mixed narcotic agonists-antagonists 7-10, by replacement of the 17-methyl groups with cycloalkylmethyl moieties. The 8 substituent modified the type of activity observed. One of these compounds, 17-(cyclobutylmethyl)-3-hydroxy-8 beta-methylmorphinan-6-one (10Ca), had an agonist-antagonist ratio of 0.1. Compound 10Ca did not support or cause dependence in rats. This compound, however, appeared to be a typical narcotic agent in morphine-dependent monkeys.

Topics: Acetates; Analgesics; Animals; Haplorhini; Humans; Mice; Morphinans; Morphine Dependence; Narcotic Antagonists; Rats; Reaction Time; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders

The analgesic activity of O-(4-methoxylphenylcarbamoyl)-3-diethylaminopropiophenone oxime hydrochloride was investigated in Swiss--Webster mice using an electroshock technique in which the pain threshold was the minimum voltage producing tonic extension of the hindlimbs in response to an electroshock delivered to the feet. The analgesic potency of O-(4-methoxylphenylcarbamoyl)-3-diethylaminopropiophenone oxime hydrochloride was equal to, or greater than, that of morphine. Neither nalorphine nor withdrawal produced visible behavioral effects in rats treated with O-(4-methoxylphenylcarbamoyl)-3-diethylaminopropiophenone oxime hydrochloride for 21 days, suggesting that the physical dependency liability of the compound may be less than that of morphine.

Topics: Analgesics; Animals; Behavior, Animal; Body Weight; Humans; Male; Mice; Morphine; Nalorphine; Oximes; Propiophenones; Rats; Reaction Time; Sensory Thresholds; Substance-Related Disorders

Topics: Animals; Central Nervous System Depressants; Codeine; Drug Evaluation, Preclinical; Haplorhini; Humans; Macaca; Macaca mulatta; Morphine Dependence; Nalorphine; Naloxone; Narcotic Antagonists; Narcotics; Self Administration; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Animals; Drug Tolerance; Endorphins; Enkephalins; History, 20th Century; Humans; Ions; Lipid Metabolism; Methadone; Morphine Derivatives; Nalorphine; Narcotics; Receptors, Opioid; Substance-Related Disorders

1 Human studies at the Addiction Research Center enable narcotic antagonists to be classified into three subgroups: (1) nalorphine-like agents; (2) pure antagonists; and (3) morphine-like agents. 2 Six narcotic antagonists (pentazocine, nalbuphine, cyclazocine, butorphanol, propiram and buprenorphine) developed in recent years seem to have a lesser abuse potential than codeine or propoxyphene. 3 When adjusted for relative availability of the agents, epidemiological data shows that pentazocine is abused less than codeine or propoxyphene in the US. 4 Recent studies with buprenorphine indicate that this agent would find application both as an analgesic of low abuse potential and as a new type of drug for the treatment of addiction.

Topics: Humans; Male; Morphine; Nalorphine; Narcotic Antagonists; Structure-Activity Relationship; Substance-Related Disorders

Rats with lateral hypothalamic self-stimulation were treated chronically with morphine (30 injections in the course of 15 days) in doses increasing stepwise from 20 to 120 mg/kg per injection. Morphine facilitated self-stimulation from the 9th injection. Both short-term abstinence (16-18 hours) and cessation of the narcotic resulted in inhibition of the response. Full suppression of self-stimulation occurred under the administration of nalorphine, morphine antagonist, in a dose of 5 mg/kg.

Topics: Animals; Depression, Chemical; Electric Stimulation; Humans; Hypothalamus; Male; Morphine; Nalorphine; Rats; Stimulation, Chemical; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Analgesics, Opioid; Animals; Benzimidazoles; Cerebral Cortex; Conditioning, Classical; Conditioning, Operant; Conditioning, Psychological; Cues; Diethylamines; Drug Tolerance; Emotions; Environment; Euphoria; Humans; Morphine; Morphine Dependence; Nalorphine; Reinforcement, Psychology; Retrospective Studies; Substance Withdrawal Syndrome; Substance-Related Disorders

A series of 53 1-phenyl-6-azabicyclo[3.2.1]octanes (1) has been tested for their analgetic and narcotic antagonist activities. Structure-activity relationships were investigated by varying the structural parameters. The most interesting compound in this series, the 1-(3-hydroxphenyl)-6,7-dimethyl derivative 8, shows the profile of a well-balanced antagonist-analgesic agent with a very mild physical dependence capacity. The absolute stereochemistry of its active enantiomer [(+)8] was established by the x-ray study and the chemical transformation to the phenylmorphan [(+)-II]. (+)-8 was stereochemically correlated also with the active enantiomer of the 7-demethyl derivatives [(+)-7] by chemical transformation and CD measurement. Certain structural and stereochemical correlations between these compounds (7 and 8) and other known antagonist-analgetics are discussed.

Topics: Analgesics; Animals; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Haplorhini; Humans; Lethal Dose 50; Macaca mulatta; Molecular Conformation; Nalorphine; Narcotic Antagonists; Rabbits; Stereoisomerism; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders; X-Ray Diffraction

Topics: Analgesia; Animals; Body Weight; Drug Interactions; Drug Tolerance; Humans; Male; Morphine; Nalorphine; Naloxone; Rats; Reaction Time; Receptors, Opioid; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

A series of morphine-like and nalorphine-like drugs were studied in the nondependent, morphine-dependent and cyclazocine-dependent chronic spinal dog. In the nondependent dog, three profiles of activity were found which could be utilized to distinguish between morphine, WIN 35, 197-2 and cyclazocine. Propiram, a prototypic partial agonist of the morphine type, produced morphine-like effects in nondependent dogs and both precipitated and suppressed abstinence in cyclazocine-dependent dogs as was needed to precipitate abstinence in morphine-dependent dogs. WIN 35, 197-2, a strong agonist in the guinea-pig ileum which has been shown to be resistant to antagonism by naloxone, neither precipitated nor suppressed morphine abstinence but suppressed cyclazocine abstinence. In the nondependent dog, it depressed the flexor reflex but not skin twitch reflex. Cyclazocine altered reflex activity much like WIN 35, 197-2 but produced tachycardia, tachypnea, mydriasis and canine delirum. The morphine and cyclazocine precipitated and withdrawal abstinence syndromes were qualitatively different. Twenty times as much naltrexone was needed to precipitate abstinence in morphine-dependent dogs. Nalorphine both precipitated and suppressed cyclazocine abstinence and appeared to be a partial agonist of the nalorphine-type. Morphine suppressed the cyclazocine abstinence syndrome. Cross-tolerance was not observed in ketocyclazocine-dependent dogs. These data are consistent with the hypothesis that there are strong and partial agonists of the mu and kappa types, and further, that physical dependence on morphine and cyclazocine is mediated through different receptors. WIN 35, 197-2 appears to be a pure strong agonist of the kappa type. Cyclazocine is a mu antagonist and mixed kappa and sigma agonist.

Topics: Animals; Behavior, Animal; Cyclazocine; Dogs; Drug Interactions; Female; Humans; Morphine; Morphine Dependence; Nalorphine; Spinal Cord; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Animals; Antitussive Agents; Aporphines; Codeine; Cough; Drug Tolerance; Guinea Pigs; Humans; Morphine; Nalorphine; Rats; Substance-Related Disorders

Topics: Adenylyl Cyclases; Cell Line; Cyclic AMP; Glioma; Humans; Hybrid Cells; Models, Biological; Morphine; Nalorphine; Neuroblastoma; Neurons; Opium; Protein Conformation; Receptors, Drug; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Hong Kong; Humans; Nalorphine; Substance-Related Disorders

Corticosteroids and ascorbic acid in the adrenal glands of adult cats have been investigated after single or repeated administration of morphine. Also plasma levels and urinary excretion of corticosteroids were determined. A significant increase in the content of corticosteroids in the glands and plasma was found after initial injection of morphine. After 7 days of consecutive morphine treatment a fall of corticosteroids in the glands was observed; after 2 weeks of daily injections the content of adrenal corticosteroids was significantly lower than in the control animals but no change was found in the plasma. Administration of the drug during 1 month led to a highly significant decrease of corticosteroids in the glands as well as in plasma. No significant change in adrenal ascorbic acids was found whether the adrenal corticosteroids were higher or lower than in the control cats. Urinary corticosteroids were high during the first week of morphine treatment but thereafter the excretion declined progressively and was lower than the control level after 13 days of treatment. The significant decrease of corticosteroids observed after repeated administration of morphine and the rise in adrenal corticosteroids found after the injection of nalorphine to the morphinized animals suggest that some kind of morphine dependence had been developed in the cats after repeated administration of the drug.

Topics: Adrenal Cortex Hormones; Adrenal Glands; Animals; Ascorbic Acid; Blood Glucose; Cats; Depression, Chemical; Female; Humans; Male; Morphine; Nalorphine; Organ Size; Stimulation, Chemical; Substance-Related Disorders; Time Factors

Topics: Amphetamine; Apomorphine; Barbiturates; Chromatography, Thin Layer; Cocaine; Codeine; Cross Reactions; Cyclazocine; Dextromethorphan; Dextropropoxyphene; Evaluation Studies as Topic; Hemagglutination Inhibition Tests; Heroin; Humans; Hydromorphone; Levorphanol; Methadone; Methods; Microchemistry; Morphine; Nalorphine; Radioimmunoassay; Spectrometry, Fluorescence; Substance-Related Disorders; Time Factors; Tritium

Topics: Animals; Brain; Cats; Dogs; Drug Tolerance; Feedback; Guinea Pigs; Haplorhini; Humans; Mice; Morphine; Nalorphine; Narcotics; Pilocarpine; Protein Biosynthesis; Rabbits; Rats; Receptors, Drug; Scopolamine; Substance-Related Disorders; Synaptic Transmission

Topics: Animals; Behavior, Animal; Body Weight; Codeine; Dose-Response Relationship, Drug; Humans; Infusions, Parenteral; Injections, Intraperitoneal; Male; Meperidine; Methadone; Morphine; Morphine Dependence; Nalorphine; Naloxone; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; Vocalization, Animal

Topics: Amobarbital; Amphetamine; Aspirin; Caffeine; Carbon Radioisotopes; Chromatography, Ion Exchange; Chromatography, Thin Layer; Cocaine; Codeine; Evaluation Studies as Topic; Glucuronates; Humans; Hydrolysis; Meperidine; Meprobamate; Mescaline; Methadone; Methods; Microchemistry; Morphine; Nalorphine; Naloxone; Pentobarbital; Secobarbital; Substance-Related Disorders

Topics: Analgesia; Analgesics; Anesthesia, Obstetrical; Asphyxia Neonatorum; Female; Fetus; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Meperidine; Morphine; Nalorphine; Naloxone; Narcotic Antagonists; Narcotics; Oxymorphone; Pregnancy; Substance-Related Disorders

Topics: Analgesics; Animals; Chemical Phenomena; Chemistry; Drug Synergism; Drug Tolerance; Haplorhini; Humans; Macaca; Molecular Conformation; Morphine; Nalorphine; Narcotic Antagonists; Phenols; Pyrrolidines; Rats; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Analgesics; Animals; Cyclazocine; Female; Haplorhini; Humans; Male; Mice; Morphinans; Morphine; Morphine Dependence; Nalorphine; Naloxone; Narcotic Antagonists; Pentazocine; Stereotyped Behavior; Substance Withdrawal Syndrome; Substance-Related Disorders; Thebaine; Time Factors

Topics: Antigen-Antibody Reactions; Chromatography, Gas; Chromatography, Thin Layer; Clinical Enzyme Tests; Electron Spin Resonance Spectroscopy; False Negative Reactions; False Positive Reactions; Fluorometry; Free Radicals; Hemagglutination Inhibition Tests; Humans; Immunoassay; Methods; Nalorphine; Narcotics; Radioimmunoassay; Substance-Related Disorders; Urine

Topics: Analgesics; Animals; Benzyl Compounds; Butylamines; Ethanolamines; Humans; Mice; Morphine; Nalorphine; Naloxone; Pyrroles; Stereoisomerism; Substance-Related Disorders

Topics: Aminopyrine; Animals; Azepines; Body Weight; Codeine; Cyproheptadine; Dextropropoxyphene; Humans; Male; Meperidine; Meprobamate; Methods; Morphine Dependence; Nalorphine; Pentazocine; Pentobarbital; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: History, 20th Century; Humans; Levallorphan; Methylation; Morphinans; Nalorphine; Narcotic Antagonists; Substance-Related Disorders

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

Topics: Cyclazocine; Humans; Levallorphan; Methadone; Nalorphine; Naloxone; Narcotic Antagonists; Substance-Related Disorders

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

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

Topics: Administration, Oral; Adult; Alcohol Drinking; Anemia, Hemolytic; Cellulitis; Chlorpromazine; Cyanosis; Dextropropoxyphene; Endocarditis, Bacterial; Germany, West; Humans; Injections, Intravenous; Male; Military Medicine; Nalorphine; Psychoses, Substance-Induced; Pulmonary Edema; Respiration, Artificial; Respiratory Insufficiency; Seizures; Substance-Related Disorders; Thrombophlebitis; United States

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: Humans; Informed Consent; Injections, Intramuscular; Injections, Intravenous; Methadone; Nalorphine; Naloxone; Substance Withdrawal Syndrome; Substance-Related Disorders

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

Topics: Conditioning, Classical; Conditioning, Operant; Conditioning, Psychological; Euphoria; Extinction, Psychological; Humans; Morphine Dependence; Nalorphine; Narcotic Antagonists; Psychotherapy; Recurrence; Reinforcement, Psychology; Self Medication; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Analgesia; Animals; Cardiovascular System; Digestive System; Humans; Male; Morphinans; Nalorphine; Respiration; Substance-Related Disorders; Urethra

Topics: Animals; Female; Fenclonine; Haloperidol; Haplorhini; Humans; Hypothalamus; Injections, Intravenous; Macaca; Methadone; Methyltyrosines; Morphine; Nalorphine; Septal Nuclei; Substance Withdrawal Syndrome; Substance-Related Disorders; Thioridazine; Trifluoperazine

Topics: Adolescent; Coma; Cyanosis; Exudates and Transudates; Humans; Hypoventilation; Injections, Intravenous; Lung Compliance; Male; Methadone; Nalorphine; Positive-Pressure Respiration; Proteins; Pulmonary Edema; Radiography; Substance-Related Disorders; Vital Capacity

Topics: Adolescent; Atrial Fibrillation; Blood Gas Analysis; Blood Pressure; Female; Heroin; Humans; Hypoxia; Intubation, Intratracheal; Levallorphan; Male; Nalorphine; Naloxone; Pneumonia, Aspiration; Positive-Pressure Respiration; Pulmonary Edema; Pupil; Respiration; Substance-Related Disorders

Topics: Breath Tests; Coma; False Negative Reactions; False Positive Reactions; Heroin; Humans; Medical History Taking; Methods; Nalorphine; Pharmaceutical Preparations; Pupil; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Humans; Levallorphan; Male; Nalorphine; Narcotics; Poisoning; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Diazepam; Humans; Injections, Intravenous; Levallorphan; Morphine Dependence; Nalorphine; Psychoses, Substance-Induced; Psychotherapy; Sleep; Substance-Related Disorders

Topics: Animals; Antibody Specificity; Carbon Isotopes; Codeine; Cross Reactions; Guinea Pigs; Heroin; Humans; Imines; Immune Sera; Lysine; Microchemistry; Morphinans; Morphine; Nalorphine; Rabbits; Radioimmunoassay; Substance-Related Disorders

Topics: Child; Child, Preschool; Female; Gastric Lavage; Humans; Infant; Injections, Intravenous; Intubation, Intratracheal; Male; Methadone; Nalorphine; Poisoning; Respiratory Insufficiency; Substance-Related Disorders

Topics: Chromatography, Gas; Chromatography, Paper; Chromatography, Thin Layer; False Negative Reactions; False Positive Reactions; Humans; Medical History Taking; Morphine Dependence; Nalorphine; Phenothiazines; Substance-Related Disorders

Topics: Analgesics; Dextropropoxyphene; Drug Antagonism; Drug Combinations; Drug Prescriptions; Drug Tolerance; Humans; Isonipecotic Acids; Methadone; Nalorphine; Narcotics; Neoplasms; Pain; Palliative Care; Substance-Related Disorders; Terminal Care

Topics: Analgesics; Animals; Bridged-Ring Compounds; Humans; Methods; Mice; Morphinans; Motor Activity; Nalorphine; Narcotics; Substance-Related Disorders

1. Rats were dosed continuously with morphine hydrochloride by giving a daily dose through tubes connected to small, subcutaneously implanted reservoirs. Morphine was withdrawn by washing out the reservoir with drug vehicle. The daily dose of morphine, or substitute drug received by each rat was determined by difference by estimating the drug remaining in reservoir washings.2. Withdrawal symptoms were more pronounced after 9 days than after 4 days of dosing with morphine.3. Body weight loss, maximal at 24 h, and increased defaecation during the first 7 h were the chief physiological signs of morphine withdrawal. The body weight loss was the result of hypodipsia and anorexia exacerbated by increased defaecation.4. When substituted for morphine in the reservoir, methadone and codeine completely prevented body weight loss and increased defaecation, while pethidine was effective against increased defaecation, but not against 24 h body weight loss. The opiate-antagonist analgesics pentazocine, nalorphine and cyclazocine either had no effect on withdrawal symptoms or increased their severity.5. In morphine dependent rats under continued morphine administration subcutaneous doses of the opiate-antagonists nalorphine, cyclazocine and naloxone all precipitated the withdrawal symptoms of body weight loss and increased defaecation. The weak antagonist pentazocine caused a significantly increased defaecation, but no significant change in body weight, while the opiates pethidine, codeine and methadone had no significant effect on body weight or defaecation.6. The advantages of inducing dependence by this method of dosing are discussed.

Topics: Animals; Body Weight; Codeine; Cyclazocine; Defecation; Female; Humans; Injections, Subcutaneous; Methadone; Methods; Morphine; Nalorphine; Pentazocine; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Anti-Bacterial Agents; Arrhythmias, Cardiac; Black or African American; Body Temperature; Coma; Drug Combinations; Ethnicity; Female; Heroin; Humans; Hypoxia; Male; Nalorphine; New York City; Pneumonia; Puerto Rico; Pulmonary Edema; Retrospective Studies; Substance-Related Disorders

Topics: Analgesics; Animals; Cyclopropanes; Humans; Injections, Intraperitoneal; Mice; Morphinans; Morphine; Nalorphine; Pentazocine; Rats; Substance-Related Disorders

Topics: Acute Disease; Administration, Oral; Adult; Coma; Female; Furosemide; Heroin; Humans; Hydrocortisone; Injections, Intravenous; Intubation, Intratracheal; Methadone; Nalorphine; Oxygen Inhalation Therapy; Penicillin G; Pulmonary Edema; Radiography; Substance-Related Disorders; Time Factors

Topics: Animals; Codeine; Electroencephalography; Hippocampus; Humans; Male; Nalorphine; Rats; Rats, Inbred Strains; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Codeine; Heroin; Humans; Levallorphan; Meperidine; Methadone; Morphine; Morphine Dependence; Nalorphine; Narcotic Antagonists; Stereoisomerism; Substance-Related Disorders

Topics: Animals; Haplorhini; Humans; Hydromorphone; Mice; Morphinans; Morphine; Nalorphine; Substance-Related Disorders

Topics: Drug and Narcotic Control; Forensic Medicine; Humans; Nalorphine; Substance-Related Disorders; United States

Topics: Animals; Brain; Dihydroxyphenylalanine; Dopamine; Female; Humans; Imipramine; Male; Methyltyrosines; Morphine; Nalorphine; Norepinephrine; Phenylalanine; Rats; Serotonin; Substance-Related Disorders; Thiocarbamates

Topics: Adult; Attitude; California; Criminal Psychology; Female; Humans; Illinois; Male; Middle Aged; Nalorphine; Psychological Tests; Psychometrics; Substance-Related Disorders

Topics: Analgesics; Animals; Antitussive Agents; Body Weight; Cardiovascular System; Constriction; Digestive System; Drug Synergism; Drug Tolerance; Humans; Hypotension; Male; Meperidine; Methods; Mice; Morphine; Nalorphine; Piperidines; Pupil; Rats; Respiration; Substance-Related Disorders; Thiopental

Topics: Animals; Body Temperature; Chlorpromazine; Drug Synergism; Female; Haplorhini; Humans; Ketones; Male; Morphine; Nalorphine; Pentobarbital; Piperidines; Substance-Related Disorders; Time Factors

Topics: Analgesia; Animals; Chemical Phenomena; Chemistry; Codeine; Haplorhini; Humans; Mandelic Acids; Morphinans; Morphine; Nalorphine; Optical Rotatory Dispersion; Stereoisomerism; Substance-Related Disorders; Sulfonic Acids

Topics: Analgesics; Animals; Azocines; Chemical Phenomena; Chemistry; Dogs; Haplorhini; Humans; Morphine; Morphine Dependence; Nalorphine; Rats; Substance-Related Disorders

Topics: Chemical Phenomena; Chemistry; Drug Antagonism; Humans; Levorphanol; Morphine; Nalorphine; Pentazocine; Substance-Related Disorders

1. Morphine-like analgesic drugs caused depression of twitches of the isolated guinea-pig ileum in response to transmural electrical stimulation. The drugs tested were the narcotic analgesics codeine, diamorphine, fentanyl, morphine, morphine-N-oxide, normorphine, oxymorphone, pethidine, phenazocine and phenoperidine and the analgesic narcotic antagonists nalorphine and pentazocine.2. With the first application of one of these drugs the extent of depression of twitches was proportional to concentration. Except in the case of pethidine, there was no further depression when additional drug was added to the organ bath. With the second application of a drug after washing out the first dose, the depressant effect was less; that is, tolerance developed. With pethidine, the depression of twitches was proportional to concentration and tolerance could not be observed.3. When tolerance had been produced by cumulative addition of these drugs, a concentration was reached at which further addition resulted in increased activity of the ileum.4. With codeine, morphine and normorphine, the twitches were increased in height and regular.5. With diamorphine, fentanyl, oxymorphone, pentazocine, phenazocine and phenoperidine there were increased but irregular responses to transmural stimulation.6. Having reached the concentration at which these effects were observed, washout of the drug resulted in reduction of activity; the twitches became smaller or the irregular responses ceased.7. Readministration of a drug after activity of the ileum had been depressed by withdrawal of that drug resulted in restoration of activity, the ileum being dependent on the presence of the drug for its activity.8. Codeine and nalorphine did not produce as great an increase in activity on readministration to a dependent ileum as did morphine: they seem to act as partial agonists in producing this effect.9. In similar experiments with the isolated urinary bladder of the rat and guinea-pig, morphine was less active in depressing responses to stimulation than it was on the ileum, and tolerance to the drug and dependence on it did not occur.10. These observations have been discussed in relation to analgesic activity, tolerance and dependence in man.

Topics: Analgesics; Animals; Codeine; Cyclic N-Oxides; Drug Tolerance; Electric Stimulation; Female; Fentanyl; Guinea Pigs; Heroin; Humans; Ileum; In Vitro Techniques; Male; Meperidine; Morphinans; Morphine; Muscle Contraction; Muscle, Smooth; Nalorphine; Oxymorphone; Pentazocine; Phenazocine; Phenoperidine; Rats; Substance-Related Disorders; Urinary Bladder

Topics: Animals; Humans; Meperidine; Methadone; Methods; Mice; Morphine Dependence; Motor Activity; Nalorphine; Substance Withdrawal Syndrome; Substance-Related Disorders

Experience with urine analysis for morphine using thin-layer chromatography in 310 cases of real or possible heroin abuse showed that it was valuable not only in detecting improper drug use but also in monitoring treatment. The results of this test can be available routinely in 24, and exceptionally in five hours. A negative result implies that the subject has taken less than 10 mg. of heroin in the past 24 hours.

Topics: Adult; Chromatography, Thin Layer; Female; Heroin; Humans; Male; Nalorphine; Physician-Patient Relations; Pupil; Substance-Related Disorders

Topics: Analgesics; Bridged-Ring Compounds; Chemical Phenomena; Chemistry; Cyclazocine; Humans; Levallorphan; Levorphanol; Morphinans; Morphine; Nalorphine; Naphthoquinones; Pentazocine; Substance-Related Disorders

Topics: Adult; Age Factors; California; Chicago; Drug and Narcotic Control; Health Surveys; Humans; Illinois; Kentucky; Nalorphine; Population Dynamics; Prisons; Substance-Related Disorders; Time Factors

Topics: Adult; Aged; Ejaculation; Heroin; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Nalorphine; Opium; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; Vomiting

The nalorphine (pupil) test for narcotic abuse is widely used in California. It is based on the ability of nalorphine to produce mydriasis in subjects who have recently taken morphine-like drugs and to produce miosis in others. The test will usually detect as little as 15 mg of morphine or comparable doses of other narcotics for several hours except in special circumstances. It is even more reliable for detection of chronic use of narcotics. A simple card pupillometer is adequate for measuring changes in pupil size resulting from nalorphine. Analysis for narcotics in urine by thin layer chromatography is also used, either alone or in conjunction with the pupil test, to detect drug abuse. In one study which included many urine speciments from subjects who had negative pupil tests the correlation between the pupil test and urinalysis was good (85 percent). When urinalysis was used to confirm suspicion of drug use resulting from a positive or equivocal pupil test, inter-method agreement dropped to about 50 percent for various reasons. Even so, use of the pupil test for screening and urinalysis for confirmation provides a satisfactory program for detection of narcotic abuse.

Topics: Chromatography, Thin Layer; Humans; Nalorphine; Pupil; Substance-Related Disorders; Urine

Topics: Dextromoramide; Humans; Male; Middle Aged; Nalorphine; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amphetamine; Barbiturates; Cannabis; Drug and Narcotic Control; Female; Heroin; Humans; Legislation, Drug; Male; Methadone; Morphine; Nalorphine; Pregnancy; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

Topics: Heroin; Humans; Methadone; Nalorphine; Substance-Related Disorders; United States

Topics: Amphetamine; California; Cocaine; Codeine; Humans; Hydromorphone; Meperidine; Methadone; Morphine; Nalorphine; Pupil; Substance-Related Disorders

Topics: Chromatography, Thin Layer; Humans; Nalorphine; Narcotics; Substance-Related Disorders; Urine

Topics: Humans; Nalorphine; Pupil; Substance-Related Disorders

Topics: Atropa belladonna; Chlorpromazine; Diagnosis; Diagnostic Tests, Routine; Humans; Meprobamate; Miosis; Morphine; Nalorphine; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Parasympatholytics; Pharmacology; Physostigmine; Pupil; Rabbits; Research; Reserpine; Substance-Related Disorders

Topics: Humans; Nalorphine; Pupil; Substance-Related Disorders

Topics: Animals; Codeine; Conditioning, Psychological; Equipment and Supplies; Haplorhini; Injections, Intravenous; Meperidine; Methadone; Morphine Dependence; Nalorphine; Opioid-Related Disorders; Rats; Substance-Related Disorders

Topics: Analgesics; Analgesics, Non-Narcotic; Antipyretics; Benzomorphans; Chemistry, Pharmaceutical; Levallorphan; Nalorphine; Pentazocine; Pharmacology; Rats; Research; Substance-Related Disorders

Topics: Animals; Autonomic Nervous System; Central Nervous System; Codeine; Nalorphine; Rats; Substance-Related Disorders

Topics: Humans; Mental Health Services; Nalorphine; Opioid-Related Disorders; Psychotherapy; Substance-Related Disorders

Topics: Humans; Nalorphine; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance-Related Disorders

Topics: Humans; Nalorphine; Substance-Related Disorders

Topics: Analgesics, Opioid; Humans; Nalorphine; Narcotic Antagonists; Substance-Related Disorders

Topics: Humans; Morphine; Nalorphine; Substance-Related Disorders

Topics: Behavior, Addictive; Methadone; Morphine; Morphine Dependence; Nalorphine; Substance-Related Disorders

Topics: Behavior, Addictive; Heroin; Humans; Male; Methadone; Morphine; Nalorphine; Substance-Related Disorders; Syndrome