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Biomedical subjects

G B Fregnan

Publications and source records attributed to G B Fregnan.

7 recordsLinked to original sources
PubMed1977

Absorption, distribution and excretion of a dihydroxydibutyl ether labelled with 14C in animals.

Kinetic studies were performed in rats, dogs and monkeys after oral administration of 14C-labelled dihydroxy-dibutyl ether (DHBE; Discinil), a known choleretic agent. The data presented indicate that the compound was intirely and readily absorbed and that it was excreted mainly with the urine in all the three species. The complete distribution pattern was investigated in rats. In most tissues high levels of radioactivity were already present after 10 min and the peak concentration was reached within the first 30 min. The decay was rapid and at the fourth hour only traces of radioactivity could be still detected in the tissues. Liver and kidney were the target organs for the radioactive material (which is in accordance with the activity and the excretory route of DHBE). The blood levels paralleled the general tissue distribution. The excretion of radioactivity was completed within 24 h in the three animal species and it took place by the urinary route, mainly witin the first 7--8 h.

Animals↗
PubMed1977

Anti-arrhytmic and general pharmacological properties of some 1,3-benzodioxole derivatives.

Seven 1,3-benzodioxole derivatives have been found to be effective against certain types of experimentally induced arrhythmias. Among them, 2-[2-(5-chloro-2-methyl-1, 3-benzodioxol-2-yl)ethoxy]-N, N-diethyl-ethanamine (LR 529) showed to be the most active. LR 529 prevented arrhythmias induced by CaCl2 intoxication in anaesthetized and conscious rats, by benzene-epinephrine in anaesthetized guinea-pigs, and by direct electrical stimulation either at increasing intensity of the ventricles of anaesthetized cats or at increasing frequency of the rabbit isolated atria. The new compound reversed to sinus rhythm the arrhythmias provoked by intoxication with aconitine and ouabain respectively in anaesthetized rats and dogs. LR 529 (and the other 1,3-benzodioxoles as well) showed scant local anaesthetic activity, short-lasting hypotensive effects, not accompanied by any change in heart rate, and discrete anti-aggregating activity on rabbit platelets "in vitro". In general, the new compounds showed weak or no effect on autonomic and central nervous systems, neither influenced other pharmacological parameters (at least within the range of doses active on experimental arrhythmias). Acute toxicity studies have indicated that even if some of the 1,3-benzodioxoles were more toxic than quinidine and procainamide, their anti-arrhythmic indexes (especially those of LR 529) were greater than those of the two reference drugs.

Anesthetics, Local↗
PubMed1976

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.

Administration, Oral↗