[Data to the pharmacology of 1-benzyl-1-(3'-dimethylamino-propoxy)-cycloheptane fumarate (EGYT-201)].
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Effects of a new beta 2-adrenoceptive agonist, BD 40A on gastric acid secretion and gastrointestinal motility were studied in comparison with those of isoproterenol, hexoprenaline and cimetidine. BD 40A (0.3 and 1 microgram/kg i.v.) inhibited dose-dependently gastric acid secretion produced by continuous i.v. infusion of tetragastrin (8 microgram/kg-hr), whereas acid secretion in response to histamine infusion (160 microgram/kg-hr) was resistant to the inhibitory action of BD 40A in pentobarbital anesthetized dogs with gastric pouches. Cimetidine (0.3 and 1 mg/kg) blocked acid secretion induced by either tetragastrin or histamine. When intraduodenally administered to pylorus-ligated rats in a dose of 1 mg/kg, BD 40A and hexoprenaline produced a reduction in acid output. Both drugs (1 microgram/kg i.v.) decreased the amplitude of gastric, duodenal and ileal motility measured by the balloon method in anesthetized dogs. The inhibitory effects of BD 40A on acid secretion induced by tetragastrin and on spontaneous motility of the gastrointestinal tract were antagonized by 1 mg/kg of propranolol. These pharmacological properties of BD 40A were qualitatively similar to those of isoproterenol and may be ascribable to the activation of beta-adrenergic receptors in the gastrointestinal tissue.
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A detailed study of kinetic peculiarities of the L-aspartate-ammonium-lyase reaction catalyzed by free and immobilized E. coli 85 cells incorporated into polyacrylamide gel, has been carried out. The effects of different types of bacterial cell "activation", substrate concentration and temperature on the reaction rate have been investigated. It was shown that the rate of the reaction is limited by the rate of the substrate transfer through the cell and cytoplasmic membranes and at sufficiently high values of the substrate can be described in terms of zero-order kinetics with respect to substrate and reaction products concentrations A kinetic model based on the diffuse and transfer processes of translocation of the aspartate-ammonium-lyase reaction participants through the cell and cytoplasmic membranes is proposed.
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General pharmacological properties of BD 40A, a new bronchodilator agent, were investigated and the following results were obtained. BD 40A showed no effect on the central nervous system, and little effect on the autonomic nervous system. BD 40A produced an increase in heart and respiration rates, a decrease in blood pressure, and change in ECG in both anesthetized dogs and conscious animals. These effects of BD 40A were inhibited by propranolol (beta-blocker) administration. BD 40A potentiated carbohydrate and lipid metabolism in Beagle dogs. The pharmacological profile of BD 40A was similar to that of hexoprenaline which was used as the reference compound.
Strains of Pasteurella multocida use L-aspartate, L-malate and furmarate, respectively, as substrates for production of succinic acid which accumulates in the medium. As was established by studies with 14C and 3H labelled substrates, the degradation of these substances proceeds analogous via the citric acid cycle.
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