Disease relevance of Vadocaine

• Moreover, spontaneous and precipitated withdrawal-induced hypothermia, weight loss and behavioural changes from repeated codeine, vadocaine and OR K-269-HCl administrations were studied [1].
• Spontaneous or precipitated withdrawal from repeated vadocaine or OR K-269-HCl administration caused neither hypothermia, weight loss nor behavioural changes [1].
• Dextromethorphan and vadocaine, both at doses of 10 and 15 mg/kg, and clobutinol (15 and 20 mg/kg) caused irreversible bradycardia and hypotension, whereas codeine (5-20 mg/kg) increased blood pressure, and to a lesser extent heart rate [2].

High impact information on Vadocaine

• Steady state pharmacokinetics of the new antitussive compound vadocaine hydrochloride [3].
• The tissue distribution of tritium-labelled vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) was studied in female mice by whole-body autoradiography at different times (15 min - 24 h) after intravenous injection [4].
• In Part I, vadocaine was compared in 20 healthy volunteers at two dose levels (10 and 30 mg) with codeine phosphate (50 mg) and a placebo [5].
• Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl) propionanilide hydrochloride, OR K-242-HCl; INN: vadocaine) is a novel antitussive compound which is effective in several animal models at doses of 2.5-6 mg/kg [6].
• At the two highest dose levels used, 400 and 500 mg, vadocaine induced side-effects originating in the central nervous system; ECG analysis revealed small prolongations in the P-Q interval and QRS complex after 400 and 500 mg [7].

Biological context of Vadocaine

• In this study, the single dose and steady-state pharmacokinetics of vadocaine hydrochloride tablet were evaluated in 28 healthy volunteers [8].
• In rats, vadocaine and lidocaine, only at the largest dose tested (64 mumol/kg i.v.), reduced mean arterial pressure (MAP), heart rate (HR) and ventilation rate (VR) [9].
• Effects of lidocaine, codeine and vadocaine hydrochloride on platelet aggregation in human platelet-rich plasma [10].

Anatomical context of Vadocaine

• In conclusion, vadocaine can be said to initiate minor deterioration of the central nervous system only at doses about 10 times higher than those which show antitussive activity [6].
• 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 [11].
• When vadocaine was given via the vertebral artery, it was about 10 times more active than by the intravenous route [11].
• 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) [11].

Associations of Vadocaine with other chemical compounds

• Urethane-anaesthetized rats and guinea-pigs were used to compare the cardiovascular, electrocardiac and ventilator effects of Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine), lidocaine hydrochloride and codeine phosphate [9].

Analytical, diagnostic and therapeutic context of Vadocaine

• The safety of vadocaine was evaluated by ECG monitoring and by hematological and biochemical laboratory tests [3].
• Antitussive action of the new anilide derivative vadocaine hydrochloride compared with codeine phosphate in four animal models [11].
• Cardiovascular and ventilator effects of vadocaine hydrochloride in urethane-anaesthetized rats and guinea-pigs [9].
• Vadocaine is sufficiently safe for future clinical trials in patients with cough [7].
• Concentrations of vadocaine in serum were around 1 microgram/ml during oral administration [11].

References