morphinans and Cough

In this report-the fourth of a series on codeine and its alternates for pain and cough relief-an attempt is made to evaluate, on the basis of experimental and clinical data, and wherever possible in comparison with codeine, the effectiveness of a number of antitussive substances currently in clinical use. In the discussion of the undesired side-effects particular attention is paid to the risk of dependence and abuse.

Topics: Alkaloids; Animals; Antitussive Agents; Cats; Codeine; Cough; Dogs; Guinea Pigs; Histamine H1 Antagonists; Humans; Isoquinolines; Meperidine; Methadone; Mice; Morphinans; Phenanthrenes; Phenothiazines; Rats; Substance-Related Disorders

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: Aged; Antitussive Agents; Clinical Trials as Topic; Codeine; Cough; Female; Humans; Male; Middle Aged; Monitoring, Physiologic; Morphinans; Placebos

Dimemorfan phosphate has been widely used for 40 years throughout the world for the treatment of coughs. This is the first report on the use of an LC-MS/MS-based assay for the determination of dimemorfan in human plasma using estazolam as an internal standard after one-step protein precipitation with acetonitrile. Chromatographic separation was achieved on a Phenomenex Luna C18 column (3 µm, 50 × 2.0 mm) using a fast gradient method, which involves water and methanol as the mobile phase (both containing 0.1% formic acid). Dimemorfan and estazolam were detected with proton adducts at m/z values of 255.8 → 155.1 and 295.0 → 267.0, respectively, in the selected reaction monitoring positive mode. The linear dynamic range of the assay was 0.04-5.00 ng/mL. The chromatographic run time for each plasma sample was <5 min. The method was proven to be accurate, precise, and repeatable. Finally, the developed method was successfully applied for the determination of dimemorfan in a pharmacokinetic study using healthy Chinese subjects.

Topics: Adolescent; Adult; Antitussive Agents; Chromatography, High Pressure Liquid; Cough; Female; Humans; Male; Morphinans; Sensitivity and Specificity; Tandem Mass Spectrometry; Young Adult

Chronic cough is defined as that which is persisting at least for trhee weeks without an evident cause. It is very common on the otorhinological practice to receive patients with chronic cough in order to rule out that their chronic cough is not produced because of an alteration in the high respiratory system. We show a clinical case with chronic cough and we make reference to the physical exploration, diagnostical method, and possibilities of medical and surgical treatment.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Antitussive Agents; Chronic Disease; Cough; Esophageal pH Monitoring; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Lansoprazole; Middle Aged; Morphinans; Radiography, Thoracic; Rhinitis, Vasomotor; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Turbinates

When co-administered intracisternally, the selective delta-opioid agonist [D-Pen2,5]enkephalin (DPDPE), which had no significant effect on the cough reflex, consistently and significantly decreased the antitussive potencies of kappa-receptor agonists, U-50,488H and U-62,066E. The decrease in the antitussive effects of these kappa-receptor agonists caused by DPDPE were prevented by selective delta receptor antagonist, naltrindole. These results suggest that delta receptors may play an inhibitory role in antitussive processes that are mediated by the kappa-receptors.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Antitussive Agents; Cough; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Indoles; Male; Morphinans; Naltrexone; Narcotic Antagonists; Pyrrolidines; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Reflex

Effects of selective mu and delta receptor agonists on capsaicin-induced cough reflex in rats were studied. Intracisternal injection (i.cist.) of a selective mu receptor agonist [D-Ala2,Mephe4,Gly-ol5]enkephalin (DAMGO) produced dose-related depression of coughs over the 0.003-0.03 nmol dose range. The antitussive potency of DAMGO was 100-fold more potent than morphine. The antitussive effects of DAMGO and morphine were significantly reduced by naloxone (1 nmol i.cist.). The selective delta receptor agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE), at a dose of 10 nmol (i.cist.), had no significant effect on the number of coughs. When co-administered i.cist., DPDPE (10 nmol) consistently and significantly decreased the antitussive potencies of DAMGO and morphine. The decrease in the antitussive effects of DAMGO and morphine caused by DPDPE were prevented by selective delta receptor antagonist, naltrindole (3 nmol). These results suggest that the antitussive effects of opioids are mediated predominantly by mu receptors, and delta receptors may play an inhibitory role in antitussive processes that are mediated by the mu receptors.

Topics: Aerosols; Animals; Antitussive Agents; Capsaicin; Cisterna Magna; Cough; Dose-Response Relationship, Drug; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Indoles; Injections; Male; Morphinans; Morphine; Naltrexone; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, mu

The possible antitussive effects of dextrorphan (the (+) isomer of levorphanol) and phencyclidine (PCP) were compared to well known antitussive properties of dextromethorphan in the post-halothane anesthetized decerebrate cat in which cough was elicited by direct electrical stimulation of the cough center. Dextrorphan, when injected i.a. (0.05-0.32 mg kg-1) or i.v. (1 to 3 mg kg-1), PCP i.a. (0.1-0.32 mg kg-1) or i.v. (1.0 mg kg-1) had no effect on electrically elicited cough. After i.v. administration, dextrorphan caused a variable effect on respiration but did not have any respiratory effect with i.a. administration of the drug. PCP injection i.a. at 0.32 mg kg-1 severely inhibited respiration though coughing could still be elicited. But i.v. administration of 1.0 mg/kg-1 suppressed both cough and respiration for several hours. Dextromethorphan inhibited cough upon both i.a. and i.v. injection. The mean effective i.a. dose was 0.063 mg kg-1. A ten times higher dose was necessary (0.65 mg kg-1) for cough suppression by the i.v. route. It is concluded from the i.a./i.v. ratio that dextromethorphan has specific central antitussive activity not possessed by dextrorphan and PCP.

Topics: Animals; Antitussive Agents; Cats; Cough; Decerebrate State; Dextromethorphan; Dextrorphan; Female; Levorphanol; Morphinans; Phencyclidine

Topics: Animals; Butorphanol; Cough; Dog Diseases; Dogs; Morphinans

Butorphanol (levo-N-cyclobutylmethyl-3, 14-dihydroxy morphinan), a potent analgetic agent of the narcotic antagonist type with a low abuse potential in laboratory animals, was evaluated for antitussive activity in unanesthetized guinea-pigs and dogs. Subcutaneously, it was over 100 times more active than codeine, dextromethorphan and dl-pentazocine and about 20 times more active than morphine in the guinea-pig, while in the dog it was 100, 10 and 4 times more active than codeine, dl-pentazocine and morphine, respectively. Orally, butorphanol was 15-20 times more active than either codeine or dextromethrophan in both species. Naloxone reversed the antitussive effects of butorphanol, codeine, morphine and dl-pentazocine while those of dextromethorphan were not antagonized. The antitussive effect of butorphanol and morphine lasted about 4 hr and both compounds were longer acting than codeine. Butorphanol was also shown to be as effective against cough of pathological origin as against experimentally induced cough in the dog.

Topics: Animals; Antitussive Agents; Bronchitis; Cough; Cyclobutanes; Dogs; Electric Stimulation; Guinea Pigs; Male; Morphinans; Naloxone; Time Factors; Tracheitis

Topics: Aerosols; Animals; Antitussive Agents; Azides; Blood Pressure; Cats; Citrates; Codeine; Cough; Dose-Response Relationship, Drug; Morphinans; Morphine Derivatives; Oxymorphone; Rats; Respiration

Topics: Acute Disease; Aged; Aging; Bronchitis; Chronic Disease; Cough; Drug Combinations; Humans; Laryngitis; Morphinans; Pentylenetetrazole; Pharyngitis; Respiratory Insufficiency

Topics: Antitussive Agents; Benzoates; Codeine; Cough; Drug Synergism; Ethics, Pharmacy; Expectorants; Histamine H1 Antagonists; Humans; Morphinans; Substance-Related Disorders; Vasoconstrictor Agents

Topics: Analgesics; Animals; Antitussive Agents; Arteries; Barium Sulfate; Blood Pressure; Body Weight; Cats; Codeine; Cough; Depression, Chemical; Dogs; Emetics; Ethers; Gastrointestinal Motility; Guinea Pigs; Humans; Mice; Morphinans; Phosphates; Rats; Respiration; Substance Withdrawal Syndrome

Topics: Analgesia; Animals; Antitussive Agents; Cats; Codeine; Cough; Guinea Pigs; Methadone; Morphinans; Morphine; Rats

Topics: Alkaloids; Animals; Antitussive Agents; Cough; Dogs; Guinea Pigs; Humans; Morphinans