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Studies on the mode of action of hexobendine, a prospective anti-anginal drug
Insights
Hexobendine increases myocardial blood flow and reduces metabolic heat production in cats at low doses. Higher doses, however, can decrease blood pressure and cardiac contractility.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Background:
- Hexobendine is a pharmaceutical compound with potential cardiovascular effects.
- Understanding its impact on myocardial function is crucial for therapeutic applications.
Purpose of the Study:
- To investigate the effects of hexobendine on myocardial blood flow, metabolic heat production, and cardiac contractility in anesthetized cats.
- To assess the protective effects of hexobendine against anoxia in isolated rabbit atria.
- To determine if hexobendine antagonizes the effects of catecholamines.
Main Methods:
- Anesthetized cats were administered varying doses of hexobendine (0.25, 0.5, and 1.0 mg/kg).
- Myocardial blood flow was measured using a heat clearance technique.
- Cardiac contractility was assessed via left ventricular pressure pulse (dp/dt) and end-diastolic pressure.
- Isolated rabbit atria were used to evaluate protection against anoxia and antagonism of catecholamine effects.
Main Results:
- Low-dose hexobendine (0.25 mg/kg) increased myocardial blood flow and decreased metabolic heat production without affecting contractility or blood pressure.
- Higher doses (0.5 and 1.0 mg/kg) reduced blood pressure and myocardial contractility (indicated by decreased dp/dt).
- Hexobendine protected isolated atria against anoxia and did not antagonize the effects of adrenaline and noradrenaline.
Conclusions:
- Hexobendine exhibits dose-dependent cardiovascular effects, enhancing blood flow at low doses and impairing contractility at higher doses.
- The compound demonstrates protective properties against anoxia and lacks significant sympathomimetic antagonism.
Abstract:
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 x 10(-6) g/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(-5) g/ml.) the increase in contractility induced by these catecholamines on isolated rabbit atria.