Mechanism of action<unk> 's dual alpha and beta adrenergic antagonism has different physiological effects in short- and long-term situations. In short-term, acute situations,<unk>  decreases blood pressure by decreasing systemic vascular resistance with little effect on stroke volume, heart rate and cardiac output. During long-term use,<unk>  can reduce heart rate during exercise while maintaining cardiac output by an increase in stroke volume.<unk>  is a dual alpha (α1) and beta (β1/β2) adrenergic receptor blocker and competes with other Catecholamines for binding to these sites. Its action on these receptors are potent and reversible.<unk>  is highly selective for postsynaptic alpha1- adrenergic, and non-selective for beta-adrenergic receptors. It is about equipotent in blocking beta1- and beta2- receptors. The amount of alpha to beta blockade depends on whether<unk>  is administered orally or intravenously (IV). Orally, the ratio of alpha to β blockade is 1:3. Intravenously, alpha to β blockade ratio is 1:7. Thus, the<unk>  can be thought to be a beta-blocker with some alpha-blocking effects. By comparison,<unk>  is a weaker β-blocker than propranolol, and has a weaker affinity for alpha-receptors compared to Phentolamine.<unk>  possesses intrinsic sympathomimetic activity. In particular, it is a partial agonist at beta2- receptors located in the vascular smooth muscle.<unk>  relaxes vascular smooth muscle by a combination of this partial beta2- agonism and through alpha1- blockade. Overall, this vasodilatory effect can decrease blood pressure. Similar to local anesthetics and sodium channel blocking antiarrhythmics,<unk>  also has membrane stabilizing activity. By decreasing sodium entry,<unk>  decreases action potential firing and thus has local anesthetic activity. Physiological action The physiological effects of<unk>  when administered acutely (intravenously) are not predictable solely by their receptor blocking effect, i.e. blocking beta1- receptors should decrease heart rate, but<unk>  does not. When<unk>  is given in acute situations, it decreases the peripheral vascular resistance and systemic blood pressure while having little effect on the heart rate, cardiac output and stroke volume, despite its alpha1-, beta1- and beta2- blocking mechanism. These effects are mainly seen when the person is in the upright position. Long term<unk>  use also has different effects from other beta-blocking drugs. Other beta-blockers, such as propranolol, persistently reduce cardiac output during exercise. The peripheral vascular resistance decreases when<unk>  is first administered. Continuous<unk>  use further decreases peripheral vascular resistance. However, during exercise, cardiac output remains the same due to a compensatory mechanism that increases stroke volume. Thus,<unk>  is able to reduce heart rate during exercise while maintaining cardiac output by the increase in stroke volume. Pharmacokinetics<unk> , in animal models, was found to cross the blood-brain-barrier in only negligible amounts.
Labetalol
Esmolol
Nadolol
Sodium nitroprusside
Nefopam
Alvimopan
Fenoldopam
Dobutamine