General Pharmacological Studies Research Articles

Pharmacological studies on Schizandra fruit. I. General pharmacological effects of gomisin A and schizandrin (author's transl)

General pharmacological studies were made on gomisin A and schizandrin which are the constituents of "Hoku-gomisi", the fruit of Schizandra chinensis BAILL. (Schizandraceae) used as an antitussive and a tonic. In the experiments by using mice, gomisin A prolonged intensively hexobarbital-induced sleeping time at doses smaller that 1/40 of LD50, inhibited spontaneous and methamphetamine-induced motor activity, and showed a hypothermic effect and at higher doses an analgesic effect by pressure pain method, while schizandrin showed the same effects except for the sleep-prolongating effect and inhibited writhing symptom by AcOH. At higher doses, both compounds showed a muscle relaxant effect. From these results, it was conceivable that the action of both compounds was a sedating or tranquilising effect. The efficacy of gomisin A was durable and intense, and that of schizandrin was transient. But on the analgesic effect gomisin A was inferior to schizandrin. Moreover, gomisin A showed an antitussive effect in guinea pigs. In the experiments by using rats, gomisin A showed inhibitory effects on gastric contraction (i.v.) and stress-induced gastric ulceration (p.o.), whereas schizandrin showed the same actions, choleretic action, and an inhibitory effect on gastric secretion. In the inhibition of gastric ulceration, the action of schizandrin was superior to gomisin A, and it was suggested that the action of gomisin A depended on the inhibition of gastric contraction to depress stressor factor, and that the action of schizandrin was mainly due to the inhibition of gastric juice secretion and gastric contraction.

General pharmacological studies of fusarenon-X, a trichothecene mycotoxin from Fusarium species

Fusarenon-X (F-X) is one of the trichothecene mycotoxins. In the present work, pharmacological properties of F-X were examined. (1) F-X induced hypothermia but did not produce appreciable behavioral changes of mice. (2) In anesthetized rats, F-X caused a rise in the blood pressure and a decrease in the respiratory rate but induced no significant change in the heart rate. (3) In isolated tissues such as fundus muscle, vas deferens, tracheal muscle, ileum, and atrium, F-X had no detectable effects on spontaneous activity and the responsiveness to agonists. (4) Subplantar administration of F-X into rat hindpaw induced edema. F-X had little influence on the histamine release from mast cells and the membrane stability of erythrocytes. (5) F-X decreased the spontaneous peristalsis of intestine but increased the intestinal propulsion of charcoal meal. (6) F-X induced vomiting in dogs which was suppressed by preliminary administration of chlorpromazine and metoclopramide. F-X may induce vomiting by stimulating the chemoreceptor trigger zone in dogs.

A survey of the pharmacological properties of metoprolol in animals and man.

Abstract: Studies in both animals and man have shown that metoprolol is a β1‐selective adrenergic receptor antagonist devoid of betamimetic activity. The cardiac stimulant effect of isoprenaline is markedly inhibited by metoprolol in doses that only slightly influence the vasodilator and bronchodilator effects of isoprenaline. Metoprolol markedly inhibits the cardiac response to exogenous or neuronally released noradrenaline. This action is probably the main determinant of the acute general hemodynamic effects of the compound. Metoprolol differs from propranolol in being a very weak inhibitor of the peripheral vasodilator effect of adrenaline. The two blockers may therefore produce differential hemodynamic effects in situations in which endogenous adrenaline contributes to cardiovascular control.Metoprolol has a preventive antihypertensive action in rats with genetically determined hypertension. This effect is associated with an impaired vasoconstrictor fibre control, the mechanism of which is discussed.The results of the toxicological and general pharmacological studies indicate that metoprolol is a highly specific β‐blocker.The pharmacokinetic studies indicate that metoprolol is completely absorbed after oral administration. The first pass elimination in man is about 55% and independent of dose in the therapeutic dose range. Metoprolol is eliminated from human blood plasma with a half‐life of 3–4 hours. The main metabolites have been isolated and characterized pharmacologically. Unchanged metoprolol appears to be responsible for the β‐blocking action.The pharmacological characterization of metoprolol gave results that warranted reformulation of the β1—β2‐receptor classification of Lands et al. (1967). This modified adrenergic β‐receptor concept is described and its implications are discussed.