levorphanol and Cough

The antitussive effects of dextromethorphan (30 mg) + salbutamol (2 mg), dextromethorphan (30 mg) alone and placebo on artificial cough induced by citric acid were compared in 19 healthy non-smoking volunteers in a double-blind crossover study. The method using inhaled citric acid with increasing concentrations to establish the cough threshold level showed an acceptable reproducibility and proved to be suitable for comparison of antitussive drugs. The cough threshold level was assessed before as well as 90 and 180 min after each medication. After placebo the cough threshold level showed no statistically significant rise. However, significant rises were shown following dextromethorphan (p less than 0.001) and the dextromethorphan-salbutamol combination (p less than 0.001). Between the treatments significant differences were shown in favour of the dextromethorphan-salbutamol combination. The results indicate that salbutamol has antitussive action enhancing the effect of plain dextromethorphan.

Topics: Adult; Albuterol; Antitussive Agents; Citrates; Citric Acid; Cough; Dextromethorphan; Double-Blind Method; Drug Evaluation; Drug Synergism; Drug Therapy, Combination; Female; Humans; Levorphanol; Male; Placebos; Random Allocation

The efficacy of an antitussive-beta 2-sympathomimetic combination (dextromethorphan-salbutamol) was compared with that of a plain antitussive (dextromethorphan) and a placebo in a double-blind trial in 108 out-patients with cough associated with acute respiratory infection. The dextromethorphan-salbutamol combination was superior to dextromethorphan or placebo in the suppression of cough at night, although a spontaneous improvement occurred in all treatment groups during the 4-day treatment period. No statistically significant differences between the treatments were shown in the symptom scores for the cough frequency and severity during the day, sputum quantity or ease of expectoration. A significant improvement in cough during the day was observed in all treatment groups. The results suggest that the use of antitussives is usually unnecessary; the only indication might be symptomatic relief, especially at night. An antitussive combined with a beta 2-sympathomimetic might be the most effective treatment in this type of cough.

Topics: Acute Disease; Adult; Albuterol; Cough; Dextromethorphan; Double-Blind Method; Drug Combinations; Dyspnea; Female; Humans; Levorphanol; Male; Random Allocation

Twenty-four inpatients affected by chronic cough completed a single-dose double-blind cross-over study of placebo, glaucine 30 mg and dextromethorphan 30 mg. The study was carried out using a balanced incomplete block design, each patient receiving two of the three experimental treatments. Objective evaluation of cough was ensured by means of a writing cough recorder. Coughs after dextromethorphan and glaucine were fewer than coughs after placebo: however only glaucine was significantly different from placebo in reducing coughs. Treatments were well tolerated: clinical results included a reduction in pulse rate after both dextromethorphan and glaucine , and a large number of patients reporting side effects after dextromethorphan administration.

Topics: Adult; Aged; Antitussive Agents; Aporphines; Clinical Trials as Topic; Cough; Dextromethorphan; Double-Blind Method; Female; Headache; Humans; Levorphanol; Male; Middle Aged; Pulse; Random Allocation; Sleep Wake Disorders; Vision Disorders

Plasma kinetics of dextromethorphan (as dextrorphan ) and codeine were investigated after acute oral doses in 8 patients with pathological cough; after which the patients participated in an acute dose-response study of the antitussive effects of each drug administered as syrups. Maximum plasma codeine concentrations averaged 384 ng.ml-1 (s.d. +/- 78.3) occurring between 0.75 and 2h after ingestion of 60 mg codeine phosphate; in comparison mean peak plasma dextrorphan levels were 386 ng.ml-1 (s.d. +/- 107.2) and 388 ng.ml-1 (s.d. +/- 101.3) respectively, after administration of 60 mg dextromethorphan syrup and tablet formulations. Bioavailability of dextromethorphan tablets was comparable to syrup. No correlation emerged between instantaneous plasma concentrations of either dextrorphan or codeine and antitussive responses; however, peak antitussive effect was significantly related to log dose with both drugs. Antitussive effects of 30 mg codeine phosphate and 60 mg dextromethorphan hydrobromide did not differ significantly; both were superior to 30 mg dextromethorphan hydrobromide and placebo.

Topics: Administration, Oral; Bronchitis; Codeine; Cough; Dextromethorphan; Dose-Response Relationship, Drug; Female; Humans; Kinetics; Levorphanol; Male; Middle Aged

Dextromethorphan, the most widely used cough suppressant in the U.S.A., was compared with codeine, the traditional European antitussive, in a double-blind, crossover trial using both an objective and subjective assessment of efficacy in sixteen patients with chronic, stable cough. Both preparations, at a dose of 20 mg, were similarly effective in reducing cough frequency. Dextromethorphan lowered cough intensity to a greater degree than codeine (p less than 0.0008) and was considered the better antitussive by the majority of patients (p less than 0.001). In view of its lack of side-effects, its safety even in overdose and its non-narcotic status, the increasing trend in Europe to use dextromethorphan as a substitute for codeine in the treatment of cough is to be welcomed.

Topics: Adult; Aged; Codeine; Cough; Dextromethorphan; Double-Blind Method; Drug Evaluation; Female; Humans; Levorphanol; Male; Middle Aged

1. Protection by codeine 20 mg, dextromethorphan 30 mg, noscapine 30 mg, and placebo against citric acid-induced cough was determined in eighteen healthy subjects. 2. Drug differences occurred at 2 1/2 h following ingestion of the drugs but not at 1 1/4 h. 3. Only coideine 20 mg had a greater antitussive action than placebo, but dextromethorphan 30 mg also did not differ from codeine 20 mg. 4. This technique may offer a useful screening test for the activity of new potential antitussive compounds in man.

Topics: Antitussive Agents; Citrates; Codeine; Cough; Dextromethorphan; Humans; Levorphanol; Noscapine; Time Factors

The present study was designed to determine whether morphine-dependent rats have a decreased sensitivity to the cough-depressant effects of both opioid and nonopioid antitussives. Morphine dependence was induced by treatment with morphine-admixed food (0.5 mg/g of food) for 7 days. The cough reflex was induced by application of electrical stimulation to the tracheal mucosa by the puncture electrode-induced cough method. The cough-depressant effect was evaluated as the antitussive ED50 calculated by the method of Litchfield and Wilcoxon. The effects of both opioid (morphine and dihydrocodeine) and nonopioid (dextromethorphan and noscapine) antitussive drugs were diminished in morphine-dependent rats. The values of ED50 of these antitussive drugs in morphine-dependent rats were about 3-fold higher than those in control rats. A significantly lower number of serotonin receptors was found in the brainstem of morphine-dependent rats (Bmax: 2.88 +/- 0.32 pmoles/mg protein) than in controls (Bmax: 4.93 +/- 0.50 pmoles/mg protein). It is possible that the decreased sensitivity to both opioid and nonopioid antitussive drugs, in terms of the depression of the cough reflex, in morphine-dependent rats may be due to changes in the number of serotonin receptors.

Topics: Animals; Antitussive Agents; Brain Stem; Codeine; Cough; Dextromethorphan; Levorphanol; Male; Morphine; Noscapine; Rats; Rats, Inbred Strains; Receptors, Serotonin

Topics: Acetyltransferases; Arylamine N-Acetyltransferase; Caffeine; Carbonated Beverages; Child; Cough; Cytochrome P-450 CYP2D6; Cytochrome P-450 Enzyme System; Dextromethorphan; Humans; Levorphanol; Metabolic Diseases; Mixed Function Oxygenases

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

Effects of antitussive drugs on the phrenic nerve activities during the cough reflex were investigated by means of a power spectrum analysis as a quantitative evaluation of each of the frequency band components of the phrenic nerve activities in anesthetized dogs. The efferent activities of the phrenic nerve were recorded from the central cut end of the phrenic nerve. Each fraction of the phrenic nerve activity was fractionated into bands spanning a range of 100 Hz each by a variable filter and analyzed using a program for the power spectrum analysis. The increase in power of each of the frequency band components was observed during the cough reflex induced by mechanical stimulation of the tracheal mucosa. Particularly, the power of the 2 approximately 100 Hz band components increased significantly as compared with the other frequency band components. An i.v. administration of codeine (3 mg/kg) significantly inhibited the increase in power of all frequency band components during the cough reflex. After administration of dextromethorphan (10 mg/kg, i.v.) or fominoben (8 mg/kg, i.v.), the increase in power of the 2 approximately 100 Hz band components of the phrenic nerve activity during the cough reflex was decreased significantly for 5 approximately 10 min; however, the other frequency band components were not affected. These results provide some evidence for a difference between these three antitussive drugs with respect to the mechanisms of action in the process of the central integration for the cough reflex.

Topics: Animals; Antitussive Agents; Codeine; Cough; Dextromethorphan; Dogs; Levorphanol; Male; Morpholines; Phrenic Nerve; Reflex

Topics: Adolescent; Animals; Antitussive Agents; Child; Child, Preschool; Codeine; Cough; Dextromethorphan; Diphenhydramine; Drug Combinations; Drug Packaging; Humans; Infant; Levorphanol; Male; Narcotics; Pediatrics; Societies, Medical; United States