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.
RCT Entities:
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: Lorenzo Leggio; George A Kenna; Anna Ferrulli; William H Zywiak; Fabio Caputo; Robert M Swift; Giovanni Addolorato Journal: Hum Psychopharmacol Date: 2011-11-16 Impact factor: 1.672
Authors: Robert E Taylor; Byron R Raysor; John Kwagyan; Vijay A Ramchandani; Nnenna Kalu; Monique Powell-Davis; Clifford L Ferguson; Lucinda Carr; Denise M Scott Journal: Alcohol Clin Exp Res Date: 2008-09-25 Impact factor: 3.455
Authors: Carolina L Haass-Koffler; Roberta Perciballi; Molly Magill; Antonella Loche; Roberto Cacciaglia; Lorenzo Leggio; Robert M Swift Journal: Psychopharmacology (Berl) Date: 2021-11-03 Impact factor: 4.530
Authors: Carolina L Haass-Koffler; Kimberly Goodyear; William H Zywiak; Lorenzo Leggio; George A Kenna; Robert M Swift Journal: Alcohol Alcohol Date: 2018-05-01 Impact factor: 2.826
Authors: ReJoyce Green; Han Du; Erica N Grodin; Steven J Nieto; Spencer Bujarski; Daniel J O Roche; Lara A Ray Journal: Alcohol Clin Exp Res Date: 2021-07-05 Impact factor: 3.928
Authors: Carolina L Haass-Koffler; Rachel D Souza; James P Wilmott; Elizabeth R Aston; Joo-Hyun Song Journal: Alcohol Alcohol Date: 2021-01-04 Impact factor: 3.913