Possible Interaction: Cocaine and Vigabatrin

“An open-label clinical trial in humans suggested that GVG may reduce cocaine and methamphetamine use.”

“In particular, animal models of both cocaine and alcohol dependence have demonstrated significant decreases in consumption of both substances after administration of vigabatrin at doses that did not impact motor activity, suggesting potential use as a therapeutic agent for cocaine or alcohol use disorders (2, 3).”

“Although no effective medication currently exists for its treatment, racemic γ vinyl‐GABA (R,S‐GVG, vigabatrin) shows enormous potential as it blocks both the neurochemical and behavioral effects of a variety of drugs, including METH, heroin, morphine, ethanol, nicotine, and cocaine.”

“Previous studies demonstrate that gamma-vinyl GABA GVG ), an irreversible GABA transaminase inhibitor, attenuates the acute rewarding effects of cocaine and other addictive drugs.”

“These data suggest …: (1) GVG significantly … cocaine- or sucrose-triggered reinstatement of reward-seeking behavior; and (2) a GABAergic-, but not dopaminergic-, dependent mechanism may underlie the antagonism by GVG of cocaine-triggered reinstatement of drug-seeking behavior, at least with respect to GVG's action on the NAc.”

“We here report that systemic administration of GVG (25-300 mg/kg) dose-dependently inhibits cocaine- or sucrose-induced reinstatement of reward-seeking behavior in rats.”

“Gabapentin (1-30 mg/kg), tiagabine (2.5-10 mg/kg) or vigabatrin (75-250 mg/kg) attenuated the cocaine (10 mg/kg)-induced hyperactivation and in the highest doses they also decreased basal locomotor activation.”

“ResultsSub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose.”

“Since sensitization may be one of the factors involved in relapse to drug use, the present results, in combination with previous findings that GVG blocks the rewarding and incentive motivating effects of cocaine , suggest that GVG might prove useful in the treatment of cocaine addiction.”

“The results of these experiments showed that GVG , at doses of 100, 200 and 300 mg/kg, reduced both ethanol and cocaine consumption in a dose-related manner.”

“In a series of microdialysis experiments in freely moving animals, S(+)-GVG (150 mg/kg), R(-)-GVG (150 mg/kg) or racemic (R, S) GVG (300 mg/kg) was administered 2.5 hours prior to cocaine (20 mg/kg) administration.”

“It was therefore important to assess if there was an enhanced toxicity from the combination of GVG with cocaine.”