Date: 2014-07-10
Type of information: Preclinical data
phase: preclinical
Announcement: preclinical results
Company: Addex Therapeutics (Switzerland)
Product: ADX71441
Action
mechanism: ADX71441 is a potent selective positive allosteric modulator (PAM) which potentiates GABA (gamma-aminobutyric acid) responses at the GABAB (gamma-aminobutyric acid subtype B) receptor. ADX71441 is a novel, first-in-class, oral, small molecules that has demonstrated excellent preclinical efficacy and tolerability in several rodent models of pain, anxiety, addiction and overactive bladder (OAB) and have also proven efficacy in a genetic model of Charcot-Marie-Tooth Type 1A disease (CMT1A). ADX71441 differs from the generic drug baclofen in that it is a positive allosteric modulator rather than an orthosteric agonist at the GABAB receptor. ADX71441 only acts when the natural ligand (GABA) activates the receptor, and therefore respecting the physiological cycle of activation.
Disease: nicotine addiction
Therapeutic area: CNS diseases
Country:
Trial details:
Latest
news: *On July 10, 2014, Addex Therapeutics, a leading company pioneering allosteric modulation-based drug discovery and development, announced positive results with ADX71441 (GABAB receptor positive allosteric modulator) in preclinical models of nicotine addiction. The results were generated as part of an ongoing research collaboration with the United States National Institute for Drug Abuse (NIDA). The study with ADX71441 examined its effects on mecamylamine precipitated physical and affective withdrawal signs in mice rendered dependent on chronic nicotine. The study was conducted as described by Jackson et al. (2008). Compared to saline-infused mice, nicotine-withdrawn mice showed a significant increased anxiety-related response, a significant increase in somatic signs and significant hyperalgesia compared to vehicle controls. Oral treatment with ADX71441 at 1, 3 and 10 mg/kg administered 60 minutes prior to the precipitant, mecamylamine, dose-dependently reversed the somatic signs of withdrawal in nicotine-dependent mice. ADX71441 also reversed hyperalgesia at the highest dose of 10 mg/kg. The highest dose of ADX71441 alone did not precipitate withdrawal anxiety-like behavior, somatic signs or hyperalgesia in saline-treated mice. Overall these data indicate that ADX71441 could alleviate the physical signs associated with nicotine withdrawal and help patients to achieve smoking cessation.
