Date: 2015-10-13
Type of information: Results
phase: preclinical
Announcement: results
Company: Addex Therapeutics (Switzerland) National Institute on Alcohol Abuse and Alcoholism (NIAAA) (USA)
Product: ADX71441
Action
mechanism: positive allosteric modulator (PAM). ADX71441 is a selective positive allosteric modulator (PAM) which potentiates GABA responses at the GABAB receptor.
Disease: alcohol use disorder
Therapeutic area:
Country:
Trial details:
Latest
news: * On October 13, 2015, Addex Therapeutics announced the statistically significant positive results in multiple preclinical models of alcohol use disorder. The data was generated as part of the ongoing collaboration with the United States National Institute on Alcohol Abuse and Alcoholism (NIAAA). Under the collaboration the pharmacology of ADX71441, a GABAB receptor positive allosteric modulator (PAM), is being evaluated in a battery of preclinical models to study its potential as a treatment for alcohol use disorder. In an alcohol self-administration model in rats, ADX71441 dose dependently demonstrated statistical significant efficacy in reducing alcohol self-administration at doses as low as 1 mg/kg i.p.. ADX71441 reduced motivation to consume alcohol in both normal and alcohol dependent animals, with a stronger effect in alcohol dependent animals. It was shown that the efficacy was due to a decrease in immediate reward rather than modulation of the caloric value of liquid reinforcers, in a self-administration paradigm using 0.2% Saccharin. In addition, it was shown that the effects were not due to sedation as locomotor activity remained unchanged up to 10 mg/kg i.p.. In models of alcohol relapse, ADX71441 blocked cue-induced relapse to alcohol seeking and blocked stress-induced relapse to alcohol seeking at all doses. It was also shown that ADX71441 attenuates neuronal activity in the central amygdala and the nucleus accumbens shell by c-Fos staining of brain slices obtained from the alcohol relapse models.
