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The biological activity of the compound Iz35, representing rigid conformer of triquinol in respect to the cardiovascular system and smooth musculature, was studied. The arterial blood pressure and heart frequency were recorded in cats and rabbits as well as the tonus of smooth musculature of bronchial tree, uterus and intestines in experiments in vivo and in vitro of rats, guinea pigs and rabbits. It was established that the compound Iz35, administered in a wide range of doses of 0.1-5 mg/kg intravenously lowered systolic arterial blood pressure, but did not change chronotropic function of the heart (statistically significantly) in contrast to isoprenaline and thymolol. The compound Iz35 and trinquinol, administered intravenously in doses off 0.01-0.1 mg/kg, manifested broncholytic effect in experiments in vivo on various models of experimental bronchospasm of guinea pigs. They had still marked spasmolytic activity (1 x 10(-9)-1 x 10(-6) g/cm2 in respect to stomach-intestinal and uterine smooth musculature. The effects of Iz35 on the cardiovascular system and smooth musculature were inhibited considerably on the background of beta-adrenergic blockade (propranolol) in comparison with triquinol. The obtained data as well as our previous studies suggest to accept that these effects of the compound Iz35 are connected mainly with affecting beta-adrenergic mediator system and it manifests double agonistic/antagonistic activity in accordance with its dose characteristic.

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Neuropharmacological study of IST was carried out on mice and rats, using the so-called practically "blind" neuropharmacological screening of M. Nikolova and L. Daleva (1968). The investigated product IST was administered under the form of 0.1-1% of solutions prepared ex tempore with saline in doses, equivalent to 1/440-1/250 to 1/2-4 1/2-4/5 of LD50. The studies on behaviour profile of mice and rats showed that IST induced symptoms of increasing inhibition of the central nervous system (CNS) in conformity with an increase in the dosage. It was established that IST inhibited dose-dependent spontaneous and stimulated with amphetamine motor activity and orientation reaction of mice, antagonized group amphetamine toxicity and excitatory effects of amphetamine as well as of morphine on mice; potentiated hexobarbital narcosis of mice and rats; lowered body temperature of rats; elevated the threshold of pentetrazolic seizures. In very high doses (50, 100 and 200 mg/kg i.p.), equivalent to 1/5 to 2/3 of LD50 IST induced excitatory effects on central and peripheral nervous system-provoked unaddressed aggressiveness, salivation, increased frequent breathing and chromodacryorrhea [correction of chromodacriurea]. The obtained experimental results show that IST manifest central depressive effect and has mainly neuroleptic character in respect to CNS.

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The antiarrhythmic activity of IST was studied on some experimental models of cardiac arrhythmia--caused by adrenaline in rats, caused by barium in non-narcotized rabbits, caused by strophanthin in guinea pigs, caused by aconitine and calcium in rats. Rhythmic disturbances were recorded by a 12-channel polyphysiograph "Galileo" or a single-channel electrocardiograph "Cardiomat". The obtained results showed that IST manifested antiarrhythmic activity in respect to adrenaline, barium and strophanthin arrhythmias without affecting substantially aconitine and calcium arrhythmias. It is thought that antiarrhythmic activity of IST, found in the indicated experimental models of cardiac arrhythmias, is most probably connected with a lowering of the peripheral sympathetic activity, realized by a central way.

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The influence of IZT on nonvascular smooth musculature in experiments in vitro was studied: on isolated intestine of the rabbit, ileum of the guinea pig, an uterine horn of the rat and guinea pig, vas deferens of the rat; as well as in vivo: on an experimental model of bronchospasm of guinea pigs, induced by acetylcholine, histamine and serotonin. Isometric contractions were recorded, and in the experiments in vivo--the tonus of the bronchial smooth musculature by a piston recorder. The obtained results showed that in experiments in vitro IZT increased the dose dependent tonus of intestinal smooth musculature; inhibited predominantly at low concentrations like clonidine the contractions of vas deferens of the rat by low frequent field stimulation--0.1 Hz and its influence was weak in respect to contractions of this organ, induced by high frequent field stimulation (10 Hz); inhibited the contractions of vas deferens in response to exogenously administered NA. IZT inhibited only bronchoconstrictor effect of serotonin in experiments in vivo. It was established that the effects of IZT both in respect to the vascular and to the nonvascular smooth musculature were Ca++ dependent and were connected with pre- and postsynaptic alpha-adrenergic receptors.

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The authors examined antiexudative activity of bioflavonoids naringin and rutin in comparative aspect in two models of acute inflammation. The experiments were carried out on 180 male white rats and 24 guinea pigs. The two flavonoids manifested marked antiexudative effect in rats with experiments peritonitis, induced by the model of U. M. Teotino et al. ED50 of naringin was 200 mg per kg after oral administration, but of rutin-260 mg per kg. In the same model ED50 of naringin was 67 mg per kg of body weight after intramuscular administration. In rats and guinea pigs with experimental lung oedema naringin, used in a dose of 200 mg per kg intraperitoneally two hours before injection of edemogenous substance (a water solution of ammonium chloride), reduced lethality with 57,4% in rats and with 37% in guinea pigs, but rutin-with 50% and 25% respectively. The examined substances were used in doses, presenting 10% of DL50. There was no statistically significant difference in respect to their antiexudative activity.

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Gentamycin acute toxicity in sexually-immature and sexually-mature male and female rats was tested comparatively. DL50 for the female sexually-mature rats was found to be statistically reliable lower than that for the remaining three groups of animals. The greatest differences were observed in the values for the maximum non-lethal and minimum lethal doses of this antibiotic. The authors suggeste the use of a new index for the evaluation of gentamycin acute toxicity called Dose Range Index.

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