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Effects of Idazoxan on Alcohol Pharmacokinetics and Intoxication: A Preliminary Human Laboratory Study
Author(s) -
HaassKoffler Carolina L.,
Leggio Lorenzo,
Davidson Dena,
Swift Robert M.
Publication year - 2015
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12658
Subject(s) - idazoxan , tolerability , placebo , pharmacokinetics , medicine , alcohol , crossover study , pharmacodynamics , anesthesia , alcohol dependence , adverse effect , psychology , pharmacology , endocrinology , antagonist , chemistry , biochemistry , pathology , receptor , alternative medicine , prazosin
Background Preliminary basic and human studies suggest that the α 2 ‐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.