Alpha-methylnorepinephrine, a selective alpha2-adrenergic agonist for cardiac resuscitation

Abstract

The selective alpha2-adrenergic agonist, alphaMNE, was as effective as epinephrine for initial cardiac resuscitation but provided strikingly better postresuscitation myocardial function and survival.

Evidence Favoring the Use of an α 2 -Selective Vasopressor Agent for Cardiopulmonary Resuscitation

“…32 Experimental studies by our group with the selective ␣ 2 -agonist ␣-methylnorepinephrine confirmed improved outcomes with fewer postresuscita- tion arrhythmias and less postresuscitation myocardial dysfunction compared with unblocked epinephrine. 33,34 When the ␣ 2 -actions of epinephrine were blocked with yohimbine, the therapeutic benefits of epinephrine for CPR were diminished. 33 The incentive to the present study was therefore to secure the rationale for a selective ␣ 2 -agonist.…”

“…33,34 When the ␣ 2 -actions of epinephrine were blocked with yohimbine, the therapeutic benefits of epinephrine for CPR were diminished. 33 The incentive to the present study was therefore to secure the rationale for a selective ␣ 2 -agonist.…”

Vasopressors for cardiopulmonary resuscitation

“…Adrenoceptors of the α1 subtype are particularly prone to desensitisation during cardiac arrest (Sun et al 2001), and, together with the potentially deleterious effects of α-adrenoceptor activation during resuscitation, this has been used as an argument for the use of selective α2-adrenoceptor agonists for resuscitation (Sun et al 2001).…”

“…The argument given is that activation of β-adrenoceptors is detrimental in resuscitation, because they increase the energy requirements of the heart, as do α1-adrenoceptors to a lesser extent. The latter also become rapidly desensitised during ischaemia (Sun et al 2001). Clonidine is unsuitable as it causes a paradoxical fall in blood pressure.…”

“…Based on the theory that α2-adrenergic receptors would be beneficial at resuscitation (Sun et al 2001), one study treated rats with carvedilol, an antagonist at 1-, 1-and 2-adrenoceptors, prior to adrenaline treatment. It was demonstrated that after induced ventricular fibrillation and adrenaline administration during resuscitation, carvedilol pre-treated animals had significantly better myocardial and neurological function than controls.…”