nalorphine and Cough

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

Effects of opioids and opioid antagonists on citric acid-induced cough and reflex bronchoconstriction have been examined in conscious guinea pigs. Airway reflexes produced by inhaled citric acid are mediated by capsaicin sensitive sensory neurons, and we examined particularly the possibility that inhibitory effects of opioids can be exerted locally in the airway. As expected, systemically administered codeine (1-10 mg/kg), meperidine (3-30 mg/kg) and morphine (1-10 mg/kg) dose-dependently inhibited cough and bronchoconstriction. However, inhalations of nebulized codeine (10-100 mg/ml) and morphine (10-30 mg/ml) also produced these effects. The potency and rapid onset of action of inhaled codeine suggest that it exerted its effects without first being metabolized to morphine. The opioid receptor antagonist naloxone completely (10-100 micrograms/kg), and nalorphine (a mixed agonist/antagonist) (1-3 mg/kg) partly, inhibited codeine's antitussive and antibronchoconstrictor effects. Nalorphine alone (3-30 mg/kg) inhibited citric acid induced reflexes, whereas naloxone was without effect. Prior inhalation of a quaternary opioid receptor antagonist, levallorphan methyl iodide (10 mg/ml), abolished the inhibitory effects of inhaled codeine (30 mg/ml). The present data suggest that inhibition of cough and reflex bronchoconstriction can be produced by opioids, acting on mu and kappa receptors located in the guinea pig tracheobronchial tree. The possible existence in the airways of a unique opioid receptor mediating inhibition of cough (as described in the central nervous system) cannot be excluded.

Topics: Animals; Bronchi; Citrates; Citric Acid; Codeine; Cough; Female; Guinea Pigs; Male; Meperidine; Morphine; Nalorphine; Naloxone; Receptors, Opioid; Reflex

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

Topics: Animals; Anthracenes; Benzoates; Codeine; Columbidae; Cough; Decerebrate State; Methadone; Nalorphine; Noscapine; Pentobarbital; Pressure; Reflex; Respiration; Time Factors

Topics: Anesthesia, Conduction; Anesthesia, Local; Animals; Antitussive Agents; Blood Pressure; Brain Stem; Bronchi; Cats; Codeine; Cough; Decerebrate State; Depression, Chemical; Dogs; Electric Stimulation; Female; Laryngeal Nerves; Male; Mice; Muscles; Nalorphine; Piperidines; Respiratory System; Sensory Receptor Cells

Topics: Analgesics; Cough; Humans; Nalorphine; Nervous System Physiological Phenomena; Reflex