Studies on the mode of action of hexobendine, a prospective anti‐anginal drug

1 . In cats anaesthetized with pentobarbitone sodium, hexobendine (0.25 mg/kg) markedly increased myocardial blood flow (measured using a heat clearance technique) and usually decreased myocardial metabolic heat production, without influencing cardiac contractility or systemic arterial blood pressure. These effects lasted for about 45 min. 2 . Larger doses (0.5 and 1.0 mg/kg) decreased systemic arterial blood pressure and the rate of rise of the left ventricular pressure pulse (dp/dt), although left ventricular end‐diastolic pressure was usually increased. This is indicative of a decrease in myocardial contractility. 3 . In a concentration of 5 × 10−6g/ml., hexobendine protected isolated rabbit atria against the decrease in contractility that follows the removal of oxygen. 4 . Hexobendine did not antagonize the systemic and myocardial effects of infusions of adrenaline and noradrenaline, nor (except in concentrations of 10−5g/ml.) the increase in contractility induced by these catecholamines on isolated rabbit atria.

[1]  J. Parratt,et al.  The effect of adrenaline, noradrenaline, and propranolol on myocardial blood flow and metabolic heat production in monkeys and baboons. , 1969, Cardiovascular research.

[2]  J. Parratt Pharmacological aspects of the coronary circulation. , 1969, Progress in medicinal chemistry.

[3]  J. Parratt,et al.  The effects of amyl nitrite inhalation on myocardial blood flow and metabolic heat production. , 1967, British journal of pharmacology and chemotherapy.

[4]  B. G. Benfey,et al.  Evaluation of sympathetic beta-receptor blockade by recording the rate of ventricular pressure rise in cats. , 1967, British journal of pharmacology and chemotherapy.

[5]  J. Parratt,et al.  A species comparison of the effects of changing perfusion pressure on blood flow and metabolic heat production in the myocardium , 1966, The Journal of physiology.

[6]  R. G. Penn SOME FACTORS INFLUENCING THE RECOVERY OF ISOLATED MYOCARDIUM FROM ACUTE ANOXIA. , 1965, British journal of pharmacology and chemotherapy.

[7]  J. Parratt A COMPARISON OF THE EFFECTS OF THE PLASMA KININS, BRADYKININ AND KALLIDIN, ON MYOCARDIAL BLOOD FLOW AND METABOLISM. , 1964, British journal of pharmacology and chemotherapy.

[8]  D. Mendel,et al.  Myocardial blood flow in the rabbit. , 1961, The American journal of physiology.

[9]  L. Hefner,et al.  The hemodynamic determinants of the rate of change in pressure in the left ventricle during isometric contraction. , 1960, American heart journal.

[10]  D. Mendel,et al.  The measurement of metabolic and vascular responses in liver and muscle with observations on their responses to insulin and glucose , 1960, The Journal of physiology.

[11]  J. Hamacher [The degree of intracardiac pressure increase in the isometric phase of spontaneous heart action as a criterion in the analysis of pharmacological effect on the warm-blooded animal heart in situ]. , 1960, Naunyn-Schmiedebergs Archiv fur experimentelle Pathologie und Pharmakologie.

[12]  J. Grayson,et al.  Factors involved in the control of cerebral blood flow , 1956, The Journal of physiology.

[13]  A. Farah,et al.  The action of some enzyme inhibitors on the isolated rabbit auricle. , 1954, The Journal of pharmacology and experimental therapeutics.