Antitussive Agent

About: Antitussive Agent is a research topic. Over the lifetime, 380 publications have been published within this topic receiving 5776 citations.

Peripheral and central sites of action of GABA-B agonists to inhibit the cough reflex in the cat and guinea pig.

Abstract: 1 The GABA-B receptor agonists baclofen and 3-aminopropylphosphinic acid (3-APPi) have antitussive activity in the cat and guinea pig. The purpose of this study was to investigate the sites of action of these GABA-B receptor agonists to inhibit the cough reflex. 2 Single intracerebroventricular (i.e.v.) cannulas were placed in the lateral ventricles of anaesthetized guinea pigs. Approximately 1 week later, the animals were exposed to aerosols of capsaicin (0.3 μm) to elicit coughing. Coughs were detected with a microphone and counted. 3 Cough was produced in anaesthetized cats by mechanical stimulation of the intrathoracic trachea and was recorded from electromyograms of respiratory muscle activity. Cannulas were placed for intravenous (i.v.) or, in separate groups of animals, intravertebral arterial (i.a.) administration of baclofen, 3-APPi, the centrally active antitussive drug codeine or the peripherally active antitussive drug BW443c. Dose-response relationships for i.v. and i.a. administration of each drug were generated to determine a ratio of i.v. ED50 to i.a. ED50, known as the effective dose ratio (EDR). The EDR will be 20 or greater for a centrally acting drug. 4 In the guinea pig, baclofen (3 mg kg−1, s.c.) and 3-APPi (10 mg kg−1, s.c.) inhibited capsaicin-induced cough by 50% and 35% respectively. The antitussive activity of baclofen was completely blocked by i.e.v. administration of the GABA-B receptor antagonist CGP 35348 (10 μg). Conversely, the antitussive effect of 3-APPi was unaffected by i.e.v. CGP 35348. However, systemic administration of CGP 35348 (30 mg kg−1, s.c.) completely blocked the antitussive activity of 3-APPi (10 mg kg−1, s.c). In separate experiments baclofen alone (1 μg, i.c.v.) inhibited capsaicin-induced cough by 78%. 3-APPi (10 and 100 μg, i.c.v.) had no effect on capsaicin-induced cough in the guinea pig. 5 In the cat, potencies (ED50) of the standards and GABA-B agonists by the i.v. route were: codeine (0.34 mg kg−1), BW443C (0.17 mg kg−1), baclofen (0.63 mg kg−1) and 3-APPi (2.3 mg kg−1). Potencies of these drugs by the i.a. route were: codeine, 0.013 mg kg−1; BW443C, 0.06 mg kg−1; baclofen, 0.016 mg kg−1; and 3-APPi, 0.87 mg kg−1. The EDRs for each drug were: codeine, 26; BW443C, 3; baclofen, 39; and 3-APPi, 3. 6 We conclude that in both the cat and guinea pig baclofen inhibits cough by a central site of action, while 3-APPi inhibits cough by a peripheral site of action.

Effect of the two tachykinin antagonists, SR 48968 and SR 140333, on cough induced by citric acid in the unanaesthetized guinea pig

Abstract: It is now well-established that sensory nerves stimulation in the airway induces bronchoconstriction and inflammation, but also protective reflexes, such as coughing. These effects are mediated through the release of tachykinins (substance P and neurokinin A) and we have recently shown that SR 48968, a tachykinin NK2-receptor antagonist, inhibited cough induced by citric acid. In this paper, we have studied the effects of SR 48968 administered by aerosol. We have also investigated the effects of SR 140333, a tachykinin NK1-receptor antagonist, and the combination of both SR 48968 and SR140333 to determine whether tachykinin NK1 receptors are involved in cough. Finally, we have studied the combined effects of SR 48968 and salbutamol to find out whether the antitussive effect of SR 48968 is a consequence of the inhibition of bronchoconstriction. Unanaesthetized guinea-pigs were placed in a transparent chamber and exposed to an aerosol of citric acid (0.4 M). The number of coughs was counted by visual inspection and by determination of sounds and pressure variations in the chamber. By the aerosol route, SR 48968 was an efficient antitussive and 16 times more potent than codeine. SR 140333 (0.1-1 mg.kg-1 i.p.) did not exert any antitussive effect but it potentiated the maximal effect induced by SR 48968. Finally, salbutamol, in a dose (0.3 mg.kg-1) which inhibits bronchoconstriction, but not cough induced by citric acid, did not modify the antitussive effect of SR 48968.(ABSTRACT TRUNCATED AT 250 WORDS)

Dextromethorphan and codeine: comparison of plasma kinetics and antitussive effects.

Abstract: 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.