noscapine and dihydrocodeine

The antitussive effect of several antitussive agents has been objectively evaluated in patients with chronic stable cough due to bronchial carcinoma, pulmonary tuberculosis or chronic obstructive lung disease. The patients received the active antitussive drugs or placebo in a double-blind, randomized crossover design. The preparations were administered at 10 p.m. and 2 a.m. on 7 consecutive nights and no antitussive was given for the following 20 hours. Cough frequency and intensity were recorded from 10 p.m. until 6 a.m. The active medications were noscapine (30 mg), dextromethorphan (20 mg), dihydrocodeine (30 mg) and codeine (20, 30 and 60 mg) at 10 p.m. and 2 a.m. Cough frequency and intensity were objectively assessed with a pressure transducer placed over the trachea and recorded on a chartrecorder. Statistical analysis was performed with analysis of variance and multiple range testing. Noscapine, dextromethorphan, dihydrocodeine and codeine (60 mg) significantly (p less than 0.001) reduced the cough frequency compared to placebo. They also produced a greater reduction of cough intensity than placebo, codeine (20 mg) and codeine (30 mg) (p less than 0.001). The duration of action of low-dose codeine (6 hours) was unsatisfactory. Subjective preference for dextromethorphan indicates a psychotropic central nervous action of this drug not assessed by the measuring device. Noscapine was equally well tolerated but more neutral psychologically.

Topics: Adult; Aged; Antitussive Agents; Bronchitis; Carcinoma, Bronchogenic; Chronic Disease; Clinical Trials as Topic; Codeine; Cough; Dextromethorphan; Double-Blind Method; Humans; Lung Neoplasms; Middle Aged; Noscapine; Tuberculosis, Pulmonary

The effects of L-tryptophan and the major constituents of cough medicines on the antitussive effect of dihydrocodeine were examined in a comparative study with anesthetized rats. The antitussive effect of dihydrocodeine was enhanced by simultaneous administration of noscapine or methylephedrine. In rats treated with noscapine and methylephedrine together, the effect of dihydrocodeine was more markedly enhanced. Furthermore L-tryptophan reduced by half the antitussive ED50 (AtD50) of dihydrocodeine. There was no difference between the AtD50 of dihydrocodeine when administered in combination with noscapine and methylephedrine and that of dihydrocodeine when combined with noscapine and L-tryptophan. The AtD50 of noscapine and dextromethorphan was also reduced by about half when what was administered with L-tryptophan. By contrast, the liability with respect to physical dependence on dihydrocodeine was not enhanced by the simultaneous administration of L-tryptophan. These results suggest that L-tryptophan can be considered to be a useful constituent of antitussive preparations.

Topics: Animals; Antitussive Agents; Brain; Codeine; Dextromethorphan; Drug Interactions; Male; Noscapine; Rats; Rats, Inbred Strains; Serotonin; Substance-Related Disorders; Tryptophan

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

The effects of noscapine and chlorpheniramine on physical dependence liability and antitussive activity of dihydrocodeine, a narcotic antitussive, were studied. For developing physical dependence, male Sprague-Dawley rats were treated with dihydrocodeine (DC), noscapine (N), and chlorpheniramine (CP) singly or simultaneously admixed with food (drug-admixed food method (DAF): DC: 0.125, N: 0.25, CP: 0.05 mg/g of food, for 7 days) or were intermittently medicated for 3 days at one-hour intervals through an implanted intravenous cannula (infusion method: DC: 0.5-2, N: 1-4, CP: 0.2-0.8 mg/kg x 24 times/day). Subsequently, rats were treated with naloxone (0.5 mg/kg, sc) and checked for withdrawal signs during 3 hours. Naloxone-precipitated body weight loss of DC was suppressed by simultaneous administration of N or CP. In combined group of DC, N, and CP, withdrawal signs, such as body weight loss, body shakes, and diarrhea, were more remarkably suppressed. Papaverine, the same kind of spasmolytic as N, was tested by the same schedule of DAF. Papaverine did not suppress the naloxone-precipitated withdrawal signs of DC. These results suggest that suppressive effect of N is not due to its spasmolytic action. On the other hand, the cough reflex was induced by electric stimulation in guinea pigs and the fifty percent of antitussive dose (AtD50) was estimated in order to evaluate the influence of N and CP on antitussive effect of DC. N and CP did not change the antitussive effect of DC. These results may suggest that N and CP suppress the development of physical dependence of DC without diminishing the pharmacological effects of DC.

Topics: Animals; Antitussive Agents; Body Weight; Chlorpheniramine; Codeine; Drug Interactions; Guinea Pigs; Male; Noscapine; Rats; Rats, Inbred Strains; Substance-Related Disorders

Topics: Antitussive Agents; Awareness; Blindness; Codeine; Cough; Double-Blind Method; Humans; Noscapine; Visually Impaired Persons