Background
Disulfiram has been an effective cocaine addiction pharmacotherapy, and one of its possible mechanisms of efficacy is through copper chelation and inhibition of an enzyme involved in catecholamine metabolism, dopamine β-hydroxylase (DβH), which converts dopamine to norepinephrine. A variant in the gene encoding DβH leads to reduced DβH activity and as such, disulfiram may not be an effective treatment of cocaine dependence for individuals with this variant. This study explored that potential matching.
Methods
Seventy-four cocaine and opioid co-dependent (DSM-V) subjects were stabilized on methadone for two weeks and subsequently randomized into disulfiram (250 mg/day, N =34) and placebo groups (N =40) for 10 weeks. We genotyped the DBH gene polymorphism, −1021C/T (rs1611115), that reduces DβH enzyme levels and evaluated its role for increasing cocaine free urines with disulfiram.
Results
Using repeated measures analysis of variance, corrected for population structure, disulfiram pharmacotherapy reduced cocaine positive urines from 80% to 62% (p = .0001), and this disulfiram efficacy differed by DBH genotype group. Patients with the normal DβH level genotype dropped from 84% to 56% on disulfiram (p = .0001), while those with the low DBH level genotype showed no disulfiram effect.
Conclusions
This study indicates that a patient’s DBH genotype could be used to identify a subset of individuals for which disulfiram treatment may be an effective pharmacotherapy for cocaine dependence.
Water-soluble diboronic acid sensor 15c exhibited higher selectivity for d-sorbitol than monoboronic acid sensor 1 and hydroxy derivative 2. And it could be applied for d-sorbitol sensing and analysis in real samples.
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