Antitussive Agent

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

Antitussive action of the new anilide derivative vadocaine hydrochloride compared with codeine phosphate in four animal models

Abstract: Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl) propionanilide hydrochloride, OR K-242-HCl; INN: vadocaine) is a novel antitussive compound structurally resembling local anaesthetics. Its antitussive profile was studied in several animal models. In guinea-pigs, vadocaine reduced by about 70% the cough episodes induced by sulphur dioxide or ammonia. The effective dose was 2.5 mg/kg p.o., and codeine phosphate was less effective. In cats, vadocaine (3 mg/kg i.v.) inhibited by about 80% for 10 min the cough reflex initiated by mechanical irritation of the trachea. When vadocaine was given via the vertebral artery, it was about 10 times more active than by the intravenous route. Codeine was 3 times as active as vadocaine by both routes. This result indicates an important central component in the antitussive action of vadocaine. In another cat model, 5 mg/kg of vadocaine was somewhat weaker than 1 mg/kg of codeine in inhibiting the cough caused by electrical stimulation of the laryngeal nerve (Domenjoz' method). In dogs, both oral and intravenous doses of 6 mg/kg of vadocaine and 2 mg/kg of codeine were approximately equiactive, inhibiting by 60-80% the cough induced by electrical stimulation of the trachea. Concentrations of vadocaine in serum were around 1 microgram/ml during oral administration. By both routes, the antitussive activity (inhibition of cough by 50% or more) lasted at least 2 h. Vadocaine caused local anaesthesia in the guinea-pig wheal preparation at concentrations of 0.25% and 0.5%, and on the guinea-pig cornea at 0.5%. Duration of anaesthesia was longer than that of lidocaine. Vadocaine did not affect the guinea-pig tracheal strip preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental studies on the antitussive properties of the new xanthine derivative 1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5-methyl-1,2,4-oxadiazol-3-yl) methyl]. 3rd communication: examinations on opioid mechanisms and physical drug dependence.

Abstract: CH-13584 (formerly: KHL-8425, 1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5-methyl-1,2,4-oxadiazol-3-yl)methyl], CAS 115779-20-9) showed antitussive effect on the citric acid spray-induced cough model. The antitussive effect of p.o. CH-13584 was antagonised by i.m. or intracerebroventricular (i.c.v.) naloxone, i.m. nor-binaltorphimine or s.c. beta-funaltrexamine. Intracerebroventricular administration of CH-13584 induced long-lasting antitussive effect which was antagonised by coadministration of i.c.v. naloxone. CH-13584 did not bind to opioid mu, delta, kappa receptor in vitro or inhibit the [3H]diprenorphine binding in vivo. Two-week treatment with CH-13584 up to the dose of 100 mg/kg p.o. did not produce autonomic and behavioural signs of withdrawal induced either by drug withdrawal or by naloxone injection, while morphine and codeine induced characteristic opioid-type physical dependence in rats.

Pharmacological treatments for sleep disorders

Abstract: This invention is directed to methods for preventing or ameliorating sleep-related breathing disorders. The method comprises administration to a patient in need thereof an effective dose of one or more antitussive agents. The antitussive agent or combination of antitussive agents can be administered in conjunction with one or more serotonin receptor agonists, one or more cannabinoid receptor agonists, one or more serotonin reuptake inhibitors, a combination of reuptake inhibitors, other agents, or any combination of the foregoing.