Showing papers on "Antitussive Agent published in 1994"

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.

Moguisteine: a novel peripheral non-narcotic antitussive drug.

Abstract: 1. The antitussive effects of moguisteine have been compared with codeine in several experimental models of cough in guinea-pigs and dogs. 2. Moguisteine and codeine dose-dependently (respective ED50 values are given in parentheses) inhibited cough induced in guinea-pigs by 7.5% citric acid aerosol (25.2 and 29.2 mg kg-1, p.o.), by 30 microM capsaicin aerosol (19.3 and 15.2 mg kg-1, p.o.), by mechanical stimulation (22.9 and 26.4 mg kg-1, p.o.) and by tracheal electrical stimulation (12.5 and 13.9 mg kg-1, p.o.). 3. Moguisteine was effective against cough induced by tracheal electrical stimulation in dogs (ED50 17.2 mg kg-1, p.o.); codeine was not tested because of its emetic effect. 4. After repeated dosing (12-15 days), moguisteine did not induce tolerance in either guinea-pigs or dogs. 5. Moguisteine did not interact with opiate receptors, since it did not show affinity for [3H]-naloxone binding sites and furthermore naloxone (5 mg kg-1, s.c.) did not antagonize its antitussive effects. 6. Moguisteine had no antitussive effect after i.c.v. administration (20 micrograms), whilst codeine (2-10 micrograms) and dextromethorphan (2.5-20 micrograms) were highly effective. 7. Our findings demonstrate that moguisteine is a novel peripherally acting non-narcotic antitussive agent, the mode of action of which remains to be elucidated fully.

Tropyl 7-azaindol-3-ylcarboxyamides as antitussive agent

Abstract: Optionally substituted pharmacologically active tropyl 7-azaindol-3-ylcarboxamides and their possible correspondent oxides, the process for their preparation and the pharmaceutical compositions containing them are described.

Pharmaceutical preparation for common cold

Abstract: PURPOSE:To provide a pharmaceutical preparation for common cold having broad drug effect and low side effect. CONSTITUTION:The pharmaceutical preparation for common cold is produced by compounding (A) one or more kinds of herb drugs having broad drug effect such as antipyretic action, analgesic action, antitussive action and antiinflammatory action and selected from SAIKO (root of Bupleurum falcatum), KAKKON (root of Pueraria lobata), SAISHIN (rhizome of Asiasarum sieboldi), ZENKO (root of Peucedanum praeruptorum) and SOYOU (leaf of Perilla frutescens) (especially preferably SAIKO) with (B) a non-herb drug such as antipyretic agent, analgesic agent, enzymatic agent, antihistaminic agent, adrenergic agent (decongestant and bronchial dilatory, antitussive agent and expectorant. A wider and stronger improving effect on common cold can be attained by the synergistic effect of the broad pharmacological action of the component A and the drug action of the component B.

Antitussive effects of levodropropizine in the dog

Abstract: The antitussive activity of levodropropizine (S(-)3-(4-phenyl-piperazine-1-yl)-propane-1,2-diol, DF 526, CAS 99291-25-5) was evaluated after oral administration to the conscious dog. Levodropropizine had a good antitussive activity, comparable with, but having a longer duration of action than dropropizine, the racemate from which it is derived. The antitussive activity of levodropropizine in the dog was approximately 1/20 of that of codeine phosphate.