Dexmedetomidine as a novel countermeasure for cocaine-induced central sympathoexcitation in cocaine-addicted humans

Andrew C. Kontak, Ronald G. Victor, Wanpen Vongpatanasin

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Cocaine-induced acute hypertension is mediated largely by increased central sympathetic nerve activity. We hypothesized that dexmedetomidine, a central sympatholytic, reverses cocaine-induced increases in sympathetic nerve activity, mean arterial pressure (MAP), and heart rate (HR) in cocaine-addicted subjects. First, we conducted a dose-finding study in 15 nontreatment-seeking cocaine-addicted subjects and 12 cocaine-naive healthy controls to find doses of intravenous dexmedetomidine that lower MAP and HR in the absence of acute-cocaine challenge. We then conducted a placebo-controlled treatment trial in 26 cocaine-addicted subjects to determine whether dexmedetomidine reverses MAP and HR increases after intranasal cocaine (3 mg/kg). Skin sympathetic nerve activity (measured in the second protocol) and skin vascular resistance (measured in both protocols) served as indices of cocaine-sensitive central sympathoexcitation. In doses up to 0.6 μg/kg IV, dexmedetomidine alone caused comparable dose-dependent decreases in blood pressure in cases and controls but a 1.0 μg/kg dose was required to lower HR. In cocaine-addicted subjects, low-dose dexmedetomidine (0.4 μg/kg; n=14) abolished cocaine-induced increases in skin sympathetic nerve activity (156±26 versus -15±22%, cocaine/placebo versus cocaine/dexmedetomidine; P<0.05), skin vascular resistance (+10±2 versus -2±3 U; P<0.05), and MAP (+6±1 versus -5±2 mm Hg; P<0.01) without affecting HR (+13±2 versus +9±2 bpm; P=ns). When dexmedetomidine was increased to 1 μg/kg (high dose; n=12) to reverse cocaine-induced increases in HR, MAP did not fall further and increased paradoxically in 4 of 12 subjects. Thus, in a low nonsedating dose, dexmedetomidine constitutes a putative new treatment for cocaine-induced acute hypertension but higher sedating doses can increase blood pressure unpredictably during acute-cocaine challenge and should be avoided.

Original languageEnglish (US)
Pages (from-to)388-394
Number of pages7
JournalHypertension
Volume61
Issue number2
DOIs
StatePublished - Feb 1 2013

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Keywords

  • adrenergic receptor agonists
  • adrenergic receptors
  • cocaine
  • sympathetic nervous system
  • sympatholytics

ASJC Scopus subject areas

  • Internal Medicine

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