Tuesday April 6, 2010
Precedex (dexmedetomidine) for Cocaine overdose?

Objectives: The aim of this study was to determine whether cocaine’s sympathomimetic actions can be reversed by a potent centrally acting 2 adrenergic receptor (AR) agonist (dexmedetomidine).

Background: We recently showed that cocaine stimulates the human cardiovascular system primarily by acting in the brain to increase sympathetic nerve activity (SNA), the neural stimulus to norepinephrine release. Thus, SNA constitutes a putative new drug target to block cocaine’s adverse cardiovascular effects at their origin.

Methods: In 22 healthy cocaine-naïve humans, we measured skin SNA (microneurography) and skin blood flow (laser Doppler velocimetry) as well as heart rate and blood pressure before and after intranasal cocaine (2 mg/kg) alone and in combination with dexmedetomidine or saline.

Results: During intranasal cocaine alone, SNA increased by 2-fold and skin vascular resistance increased from 13.2 ± 2.3 to 20.1 ± 2.2 resistance units while mean arterial pressure increased by 14 ± 3 mm Hg and heart rate by 18 ± 3 beats/min (p less than 0.01). Dexmedetomidine abolished these increases, whereas intravenous saline was without effect. Dexmedetomidine was effective in blocking these sympathomimetic actions of cocaine even in all 7 subjects who were homozygous for the Del322-325 polymorphism in the 2C AR, a loss-of-function mutation that is highly enriched in blacks.

Conclusions: The data advance the novel hypothesis that central sympatholysis with dexmedetomidine constitutes a highly effective countermeasure for cocaine’s sympathomimetic actions on the human cardiovascular system, even in individuals carrying the 2CDel322-325 polymorphism.


Central Sympatholysis as a Novel Countermeasure for Cocaine-Induced Sympathetic Activation and Vasoconstriction in Humans - J Am Coll Cardiol, 2007; 50:626-633