Study summary · research use only
Anti-hypertensive treatment preserves appetite suppression while preventing cardiovascular adverse effects of tesofensine in rats
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This rat study examined the anorexigenic and cardiovascular effects of tesofensine, a triple monoamine reuptake inhibitor in development for obesity, using a combined real-time food intake and cardiovascular telemetry monitoring system in telemetrized conscious rats. Acute tesofensine caused a dose-dependent hypophagic effect along with increased heart rate and blood pressure. Metoprolol (β1 adrenoceptor blocker, 10-20 mg/kg, p.o.) prevented the cardiovascular sympathetic effects of tesofensine while leaving its inhibitory effect on food intake unaffected; telmisartan (angiotensin AT1 antagonist, 1.0-3.0 mg/kg, p.o.) did not interfere with the anti-obesity effects but only partially reversed the systolic blood pressure increase and had no effect on elevated heart rate. The authors suggest tesofensine raises heart rate and blood pressure via sympathetic activity, with different adrenoceptor subtypes potentially responsible for its anti-obesity and cardiovascular effects.
Abstract
Tesofensine is a novel triple monoamine reuptake inhibitor which is in development for the treatment of obesity. Preclinical and clinical data suggest that appetite suppression is an important mechanism by which tesofensine exerts its robust weight reducing effect. Notably, the strong hypophagic response to tesofensine treatment is demonstrated to be linked to central stimulation of noradrenergic and dopaminergic neurotransmission. The sympathomimetic mode of action of tesofensine may also associate with the elevated heart rate and blood pressure observed in clinical settings, and we therefore sought experimentally to address this issue. The anorexigenic and cardiovascular effects of tesofensine were studied simultaneously in telemetrized conscious rats in a combined real-time food intake and cardiovascular telemetry monitoring system. Acute administration of tesofensine caused a dose-dependent hypophagic effect as well as increased heart rate and blood pressure. Interestingly, combined treatment with metoprolol (b1 adrenoceptor blocker, 10-20 mg/kg, p.o.) fully prevented the cardiovascular sympathetic effects of tesofensine while leaving the robust inhibitory efficacy on food intake unaffected. Similarly, the angiotensin AT1 receptor antagonist telmisartan (1.0-3.0 mg/kg, p.o.) did not interfere with the anti-obesity effects of tesofensine, however, telmisartan only partially reversed the increase in systolic blood pressure and had no effect on the elevated heart rate induced by tesofensine. These data suggests that tesofensine causes elevations in heart rate and blood pressure by increasing sympathetic activity, and that different adrenoceptor subtypes may be responsible for the anti-obesity and cardiovascular effects of tesofensine.
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