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An experimental model of the "withdrawal syndrome" in chronic clonidine treatment is reproduced in spontaneously hypertensive rats (SHR). Medication is withdrawn abruptly after daily oral administration of 100 micrograms/kg clonidine for 12 days or after it has been received with the drinking water in a dose of approximately 250 micrograms/kg daily for 14 days. In the course of the treatment, as well as on the 24th and 48th hour after withdrawal, studies are carried out of the changes in the arterial pressure, heart rate, vascular resistance, the contractions of electrically stimulated m.anococcygeus and vas deferens, as well as some biochemical parameters (noradrenaline content in the brain and myocardium, the level of glucose and free fatty acids in the blood, the activity of phosphorylase "a" in the myocardium). In the course of clonidine treatment there is potentiation of the peripheral noradrenaline effects on the arterial pressure and vascular resistance, increasing hyperglycaemia, reduced noradrenaline content in the brain and myocardium, as well as potentiation of the inhibitory effect of clonidine on the contractions of electrically stimulated m.anococcygeus, as well as potentiation of the isoprenaline responses on the arterial pressure. The isoprenaline effects on electrically stimulated vas deferens, as well as the activity of the stimulated phosphorylase "a", decrease. No sharp increase in the arterial blood pressure was observed upon withdrawal of the clonidine treatment. The reactivity of the peripheral pre- and postsynaptic alpha-adrenergic receptors is intensified (the effects of noradrenaline on the arterial pressure and vascular resistance become even stronger, the noradrenaline content in the brain and myocardium and hyperglycaemia increase, and there is potentiation of the inhibitory effect of clonidine on electrically stimulated m.anococcygeus.(ABSTRACT TRUNCATED AT 250 WORDS)

The article studies the pharmacological properties and the toxicity of the original theophylline derivative G112: 7-/2-bis-/2-hydroxy-ethyl/-aminoethyl/-1,3-dimethylxanthine tartarate, synthesized by Y. Gagaouzov and P. Peykov. Considerable bronchorelaxing activity, measurable with novphylline, has been found in experiments in vivo, as well as in isolated tracheal preparations contracted by various spasmogens. In equimolar concentrations the compound has a weaker inhibitory effect on the phosphodiesterase in the lungs and the brain, compared with theophylline, and it almost does not activate the myocardiac phosphorylase "a" and the lipolysis. A weak and brief hypotensive effect has been established, moderate diuretic action and excitatory effect on the central nervous system, similar to that of novphylline. The compound has considerably lower toxicity than novphylline and it does not lead to changes in the body weight and in the basic haematological and biochemical parameters after treatment of rats for three months.

The antiarrhythmic activity of the compound N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphthyl)-N-(3-oxo-3-phenyl-2-methylpropyl)-piperazine hydrochloride, referred to as P11, is studied on anaesthesized cats and Wistar albino rats, as well as on non-anaesthesized rabbits. Four types of experimental arrhythmia are used--with BaCl2, with chloroform-adrenaline, with strophantine G and with aconitine. The compound P11 is introduced in doses of 0.25 and 0.50 mg/kg intravenously and 10 mg/kg orally. The compound manifests antiarrhythmic activity in all models of experimental arrhythmia used, causing greatest inhibition on the arrhythmia induced by chloroform-adrenaline (in 90 per cent) and with BaCl2 (in 84 per cent). The results obtained are associated with the beta-adrenoblocking and with the membrane-stabilizing action of the compound.