title: Effects of idazoxan on alcohol pharmacokinetics and intoxication: a preliminary human laboratory study.
abstract: BACKGROUND
  Preliminary basic and human studies suggest that the α2 -adrenergic antagonist idazoxan may represent a novel medication for alcohol dependence. The goal of this study was to evaluate the safety and tolerability of the co-administration of idazoxan with alcohol and explore whether pharmacokinetics (PK) and biobehavioral mechanisms of idazoxan may alter alcohol's effects.
  
  
  METHODS
  This was a preliminary double-blind, single-dose, placebo-controlled, crossover, randomized human laboratory study. Ten social drinkers were dosed, in 2 different alcohol challenge studies (ACS), with a single oral dose of idazoxan (40 mg) or placebo, followed by a fixed alcohol dose 60 minutes later. Participants returned after a 1-week washout, and they were crossed over to the opposite medication condition.
  
  
  RESULTS
  There were no significant differences in adverse events between idazoxan and placebo. Moreover, during the ACS paradigm, 40 mg idazoxan was well tolerated with no significant autonomic effects compared to placebo; idazoxan reduced the peak blood alcohol level (p < 0.01) and time to peak (p < 0.05) compared to placebo. A PK/pharmacodynamic model aligned the biobehavioral effects, demonstrating that the co-administration of 40 mg idazoxan with alcohol decreased alcohol-related stimulation (p < 0.05) and increased alcohol-related sedation (p < 0.05).
  
  
  CONCLUSIONS
  This study supports the safety and tolerability of 40 mg idazoxan when co-administered with alcohol. Additionally, this study suggests that idazoxan may alter the biphasic effects of alcohol by decreasing stimulation and increasing sedation. These findings have implications for further investigation of using idazoxan as a probe to develop potential novel medications to treat alcoholic patients.
authors.affiliation: Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, Rhode Island.
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Haass-Koffler
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leggio
authors.forename: Dena
authors.initials: D
authors.lastname: Davidson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Swift
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000009:adverse effects / Q000494:pharmacology; D000328:Adult; D000435:Alcoholic Intoxication / Q000175:diagnosis*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D000431:Ethanol / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D019329:Idazoxan / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D055815:Young Adult
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000431:Ethanol; D019329:Idazoxan
keywords: Alcohol Challenge Study; Idazoxan; Norepinephrine; PK/PD Alcohol Model
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