A randomized controlled study of the effect of ifenprodil on alcohol use in patients with alcohol dependence

Abstract

Aim: This prospective, randomized, controlled, rater-blinded study investigated the effect of G protein-activated inwardly rectifying potassium (GIRK) channel inhibitor ifenprodil on alcohol use in patients with alcohol dependence. Methods:The participants were 68 outpatients with alcohol dependence who were assigned to an ifenprodil group (administered 60 mg ifenprodil per day for 3 months) or control group (administered 600 mg ascorbic acid and calcium pantothenate per day for 3 months). The participants completed a questionnaire that included the frequency of alcohol drinking and presence of heavy drinking before the study period (time 1) and 3 months after the start of the study period (time 2).The alcohol use score was calculated using these two items.Results: Valid data were obtained from 46 participants (25 in the ifenprodil group and 21 in the control group). The alcohol use score at time 2 in the ifenprodil group was significantly lower than that in the control group after adjusting for the score at time 1 and some covariates. The intention-to-treat analysis of multiply imputed datasets indicated similar results. Group differences in the frequency of alcohol drinking were significant in the multiply imputed datasets but not in 46 participants. The ifenprodil group had a significantly lower rate of heavy drinking at time 2 than the control group.Conclusions: This study found an inhibitory effect of ifenprodil on alcohol use in patients with alcohol dependence. The results support the hypothesis that GIRK channel inhibitors ameliorate alcohol dependence.Trial registry: This trial was registered in the UMIN clinical trial registry (UMIN000006347).alcohol dependence, alcohol use, G protein-activated inwardly rectifying potassium channel, ifenprodil, randomized controlled study Nagisa Sugaya and Yasukazu Ogai contributed equally to this study.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. The rewarding effects of addictive substances are mediated by various molecules, and much attention has been given to the effects of G protein-activated inwardly rectifying potassium (GIRK) channels. 4 GIRK channels play an important role in signaling that is influ- The opening of GIRK channels hyperpolarizes the cell membrane to modulate neuronal excitability. Ethanol has been found to directly open GIRK channels. [8][9][10] Nucleotide sequence differences in GIRK channel subunit genes have been reportedly related to alcohol dependence and other substance use disorders. Ethanol-induced antinociception is reduced in weaver mutant mice that possess an amino acid sequence mutation of the GIRK2 subunit. 5,8 Hill et al 11 reported that GIRK2 knockout mice exhibited a reduction in saccharin aversion at a nonhypnotic dose of ethanol in a conditioned taste aversion paradigm and weaker ethano...

Study of effects of ifenprodil in patients with methamphetamine dependence: Protocol for an exploratory, randomized, double‐blind, placebo‐controlled trial

“…First, this study is the first clinical trial of ifenprodil treatment for patients with methamphetamine dependence in a double‐blind, placebo‐controlled trial. Because the previous study of ifenprodil treatment for patients with alcohol dependence was conducted with a prospective, randomized, controlled, rater‐blinded design, the patients were able to recognize which drug they received (ifenprodil [Cerocral] or control drug [Cinal]) based on the receipt they received at the time of accounting in the healthcare system in Japan. Thus, we presumed that this previous study may not be sufficient to assess the efficacy of ifenprodil treatment.…”

“…Second, the patient sample in the present study is not limited to patients who can be prescribed with ifenprodil based on insurance coverage. The subjects in the previous study were limited to patients with alcohol dependence who were suspected of having mild cognitive deficiency or brain damage because these patients can be prescribed with ifenprodil based on insurance coverage . These limited inclusion criteria in the previous study may have precluded an accurate evaluation of the efficacy of ifenprodil treatment.…”

“…The SRRS is composed of five subscales: anxiety and intention to use drug, emotionality problems, compulsivity for drug use, positive expectancies, and lack of control over drug use and lack of negative expectancy for drug use . A higher average total score and higher subscale score indicate higher relapse risk …”

“…40 A higher average total score and higher subscale score indicate higher relapse risk. 37,40 Drug craving during the 84-day administration period will be assessed by the NRS. A previous study used visual analog scales (VASs) to assess craving for drugs.…”

“…Ifenprodil has been used broadly in clinical practice in Japan. A recent study reported that ifenprodil treatment (60 mg/d) for 3 months decreased alcohol use scores in patients with alcohol dependence compared with patients who received the control medication (Cinal) . Hori et al showed that 120 mg/d ifenprodil effectively reduced craving in a patient who used Bron ® (SSP Co., Ltd., Tokyo, Japan) cough medicine and in a patient with alcohol dependence.…”