Pharmacology of dihydroxy-dibutylether, a specific choleretic drug

The choleretic and the general pharmacological properties of dihydroxy-dibutyl ether (Discinil) were investigated in several animal species. Discinil (DHBE) increased the bile flow in conscious rats and dogs, after both oral and i.v. administration. A choleretic effect was also observed after i.v. injection into anaesthetized rats and guinea pigs. A dose-response relationship was always obtained, the threshold dose being 25--100 mg/kg. No evidence of tachyphylaxis was observed in rats after repeated treatments. The bile hyperflow was generally accompanied by an increased excretion of the total dry residue in guinea pigs and dogs. The choleretic effect in rats was still present after pretreatment with either DL-ethionine (causing parenchymal liver damage) or atropine (blocking the cholinergic control of bile production). At low doses (25--100 mg/kg i.v.) eliciting a definite choleretic response, DHBE did not show spasmogenic and spasmolytic effects in vivo on the smooth muscles of the gallbladder of guinea pigs and dogs, neither on the stomach and intestine of mice and dogs; while it constricted the pylorus sphincter of rats. At larger doses (200--400 mg/kg i.v.) the compound showed a mild relaxing activity on Oddi's sphincter of guinea pigs and a weak spasmogenic activity either on gall bladder or on small intestine. In vitro, it caused an unspecific antagonism against the spasm induced by acetylcholine, barium chloride, histamine, 5-hydroxytryptamine and norepinephrine. In anaesthetized rats, rabbits and dogs, DHBE caused a moderate and short-lasting hypotension, and tachycardia. The threshold doses for these effects were 2--4 times superior to those being choleretic. In conscious dogs, the compound was slightly hypertensive. DHBE did not provoke important respiratory and ECG changes, neither showed diuretic nor antiphlogistic effects.