Showing papers on "Antitussive Agent published in 1988"

Antitussive properties of levodropropizine.

Abstract: The antitussive activity of levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), was evaluated in anaesthetized guinea-pigs and rabbits and in unanaesthetized guinea-pigs. Levodropropizine was shown to have good antitussive activity. Intravenously, it was 1/10 to 1/20 as active as codeine and comparable to dropropizine, from which it is derived, on mechanically and electrically induced coughing in rabbits and guinea-pigs. After oral administration to the guinea-pig the antitussive activity of levodropropizine was comparable with those of both dropropizine and codeine against coughing induced by irritant aerosols.

Effects of Double-enkephalin (Biphalin), an Enkephalin Analogue, on Respiration and the Cough Reflex in Rats

Abstract: The pharmacological actions of double-enkephalin (biphalin ; (HCl-Try-D-Ala-Gly-Phe-NH-)2) an analogue of enkephalin, on nociception, respiration and the cough reflex were compared with those of morphine in anesthetized rats. Double-enkephalin (D-Enk), injected i.p., produced significant analgesia at doses of 10 and 20 mg/kg in a hot-plate test. The analgesic effect of D-Enk was antagonized by pretreatment with naloxone (5 mg/kg, i.p.). D-Enk and morphine (M) produced a dosedependent decrease in the frequency of respiration (RF) and in the tidal volume (Vt). However, the effects of D-Enk on RF and Vt were significantly weaker than those of M. The 50% antitussive dose (AtD 50) of D-Enk and M were 0.63 and 0.48 mg/kg, i.p., respectively. The antitussive effect of D-Enk was antagonized by pretreatment with naloxone (0.4 mg/kg, i.p.). These results suggest that D-Enk exerted an antitussive effect similar to that of morphine, and that the involvement of opiate receptors is associated with the antitussive effect of D-Enk.

Antitussive activity and respiratory system effects of levodropropizine in man.

Abstract: Antitussive activity of the new antitussive drug, levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), was evaluated in healthy volunteers by the classical method of citric acid-induced coughing. Levodropropizine dose-dependently reduced cough frequency. Maximal inhibition was observed at 6 h after administration. Cough intensity was also reduced, as shown by the analysis of cough noise. Levodropropizine, at the dosage of 60 mg t.i.d., had no adverse effects on respiratory function nor on airway clearance mechanisms: in fact, it did not affect spirometric parameters. Levodropropizine had no effects on the rheological properties of mucus nor on ciliary activity of airway epithelium.

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)

The effects of noscapine and chlorpheniramine on physical dependence and antitussive activity of dihydrocodeine

Abstract: 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.

Synthesis and pharmacological screening of new phenylpiperazinepropane derivatives and their enantiomers.

Abstract: Enantiomers of phenylpiperazinepropane-1,2-diol derivatives were synthesized with the purpose to obtain a better antitussive activity/sedative effect ratio. (S)-isomers showed better pharmacological profiles than (R)-isomers and corresponding racemates. Among the (S)-isomers, the unsubstituted compound, levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), has the most favourable antitussive activity/sedative effect ratio and was selected for pharmaco-toxicological evaluation.

First human studies on the safety and antitussive activity of vadocaine hydrochloride

Abstract: Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) is a new anilide derivative which resembles lidocaine in chemical structure The safety and antitussive effects of this new compound were studied in 6 healthy male volunteers in the first Phase I clinical trial Vadocaine was administered in single doses of 5, 10, 15, 20, 30 and 50 mg At these dose levels vadocaine had no effects on the cardiovascular system, the haematological variables, blood biochemistry or urinary sediment examined as safety evaluation The antitussive properties of the compound were studied using inhaled citric acid for induction of the cough response The antitussive properties of vadocaine were most effective at a dose of 15 mg, although no statistical significance was found Neither was any dose-response relationship noted However, at this dose level vadocaine is apparently safe and its antitussive properties seem promising enough for further evaluation