Single-Dose Interaction Study of the Arginine Vasopressin Type 1B Receptor Antagonist ABT-436 and Alcohol in Moderate Alcohol Drinkers

Background ABT‐436, a potent and selective arginine vasopressin (AVP) type 1B receptor (V1B) antagonist, has previously demonstrated basal hypothalamic–pituitary–adrenal (HPA) axis attenuation in man. A V1B antagonist is hypothesized as an alcohol‐dependent treatment based on the role of the V1B receptor in stress regulation and the finding that stress is a trigger for relapse in alcoholics. A V1B antagonist has shown favorable effects in rat models of alcohol dependence. A single‐dose clinical study was conducted to assess the potential for pharmacokinetic or pharmacodynamic interaction between ABT‐436 and alcohol. Methods Twenty moderate alcohol drinkers each received the 4 possible combinations of a single 1,000 mg ABT‐436 dose (or matching placebo) and a single 0.5 g/kg alcohol dose (or placebo for alcohol) in a double‐blind, randomized, 4‐period crossover study. Plasma ABT‐436 and blood alcohol levels were measured to assess pharmacokinetic interactions. A computerized cognitive test battery (CDR System), Bond–Lader Visual Analog Scales scales, and a postural stability test were used to measure the effects of alcohol and the potential interaction with ABT‐436. The pharmacologic effect of ABT‐436 was assessed by measuring serum cortisol. Results Neither ABT‐436 nor alcohol affected the blood levels of the other. Alcohol reduced performance on 2 of 5 CDR System composite variables (power of attention, p = 0.002; quality of secondary episodic memory, p