Journal de pharmacologie最新文献

The mechanisms by which isoprenaline and prenalterol increase heart rate and myocardial contractile force were investigated in conscious instrumented dogs. Isoprenaline (0.1 micrograms/kg/min/10 min) increased both heart rate (+98 +/- 14%) and contractility (+36 +/- 5%) and decreased diastolic blood pressure. beta 1-Adrenoceptor blockade abolished the isoprenaline induced increase in contractility whereas the induced tachycardia was reduced by approximately 50%. Either beta 2-blockade, which abolished the hypotensive effect of isoprenaline or ganglionic blockade, which abolished the isoprenaline-induced activation of sino aortic baroreflexes, strongly reduced (-67 +/- 8%) the isoprenaline-induced tachycardia but did not markedly alter the increase in contractility. However, the isoprenaline-induced increase in contractility was potentiated by methylatropine (+83 +/- 12%) whereas the simultaneous tachycardia was less marked than before methylatropine. In the same dogs, prenalterol (2 micrograms/kg/min/5 min) increased contractility (+38 +/- 5%) to the same extent as isoprenaline but induced a lesser increase in heart rate (+23 +/- 3%) and had no effect on aortic pressure. These effects were not significantly modified by pretreatments with either ganglionic or beta 2-blockades but were abolished by beta 1-blockade. After methylatropine the prenalterol-induced increase in heart rate was not modified but the increase in contractility was potentiated (+63 +/- 11%). We conclude that whereas indirect activation of arterial baroreflexes through hypotension markedly contributes to the isoprenaline-induced increase in heart rate, the simultaneous increase in cardiac inotropism is only dependent upon direct beta 1-adrenoceptor activation by isoprenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

By the determination of the free concentration of a drug using the equilibrium dialysis method, a volume shift could be observed, inducing a dilution of the protein medium. The value of this volume shift varies with the plasmatic sample and could produce a misdetermination of the free fraction which could be important, essentially for the drugs strongly bound to proteins.

The effects of medroxalol, a new beta-blocking drug, were simultaneously studied on the brachial artery, the arterioles and the veins of the forearm in 15 patients with mild to moderate essential hypertension after administration of a single oral dose of 200 mg, by means of pulsed Doppler velocimetry of the brachial artery and strain gauge mercury-in silastic plethysmography of the forearm. In addition the systolic time intervals including preejection period (PEP) and left ventricular time (LVET) were also measured after drug administration. Acute oral medroxalol produced a rapid and significant decrease in systolic and diastolic blood pressure and in heart rate. Concomitantly a significant increase was observed in brachial artery diameter (p less than 0.05), blood velocity and flow (p less than 0.01); forearm vascular resistance decreased (p less than 0.001) but forearm venous tone was unchanged. Lastly medroxalol prolonged PEP but shortened LVET corrected for heart rate. These results demonstrate a rapid antihypertensive action of a single dose of medroxalol with a dilation of the arteries but not of the veins of the forearm and a discrepant effect on the systolic time intervals.

Among the antimalarial drugs, chloroquine (CLQ) and 4-aminoquinoline derivatives display important interferences with biological membranes. The present study reports the effects of CLQ on dihydropyridine binding sites, measured in the heart of rats intoxicated with the drug. Acute intoxication does not entail any modification of the sites. On the other hand, binding sites were dramatically decreased by a chronic intoxication realized twice a week. In such a case, this decrease may be directly related to CLQ concentration in the heart. The regulation mechanisms involved are discussed.

In the tail suspension test (TST), the rat is suspended by the tail for 6 min during which the animal shows periods of agitation and immobility. The duration of the immobility is measured. Desipramine decreased the duration of immobility. The main advantages of this procedure are: the use of a simple, objective test situation; the concordance of the results (for desipramine) with the "behavioral despair" test described by Porsolt; the avoidance of the hypothermia induced by immersion in the Porsolt test.

Experimental and clinical studies demonstrate the antifibrillatory effectiveness of bretylium tosylate: Experimental ventricular fibrillation induced either by electrical stimulation or by ischemia is prevented by bretylium. In 2,000 acute myocardial infarction patients who received bretylium prophylactically primary ventricular fibrillation occurred in less than 1% of cases. In a randomized hemodynamic study in acute myocardial infarction patients bretylium induced a significant decrease in heart rate, systolic and mean left ventricular pressures, and in systolic and mean aortic pressures. In addition, a parallel and significant decrease in total pulmonary and systemic resistances was seen, accompanied by decreases in tension time and left ventricular (delta P/delta V) indexes. Bretylium tosylate induces stabilization of electrical systole duration (QTc) in acute myocardial infarction patients. The conclusions of the present review strongly support those of the United States Food and Drug Administration, approving bretylium for prophylaxis and treatment of ventricular fibrillation.

The antagonist effect of various antidepressants, both tricyclic and non-tricyclic, and of thiothixene on the histamine H2 receptors has been studied in the rat isolated uterus. All the drugs studied inhibit the effect of histamine, acting as competitive antagonists. Trimipramine and mianserin were the antidepressants which showed the highest activity, superior to cimetidine, whereas nomifensine, viloxazine, trazodone and maprotiline were those which showed the lowest antihistamine H2 activity. These results suggest that there is an interaction between antidepressants and histamine H2 receptors in rat isolated uterus similar to the interaction existing between antidepressants and histamine H2 receptors in brain and other tissues.