Addex Pharmaceuticals, the allosteric modulation company, announced that ADX71943 has demonstrated statistically significant analgesic-like effects in three preclinical models of pain.
In the first model, ADX71943 reversed complete Freund adjuvant (CFA)-induced reductions in withdrawal thresholds in a dose-related manner, with a minimum statistically significant effective oral dose of 10 mg/kg. In a second model (Formalin test), ADX71943 showed anti-nociceptive effect after oral administration of 3 to 10 mg/kg. In a third model, an increased visceral pain threshold was seen using ADX71943 with a minimum statistically significant effective dose between 3 and 10 mg/kg.
ADX71943 is an orally available positive allosteric modulator (PAM) of the GABA(B) receptor that has potential for treatment of osteoarthritis pain and chronic nociceptive pain as well as other indications. ADX71943 has a good developability profile and is expected to enter clinical testing in the fourth quarter 2010.
"We are impressed with the profile of the compound and by its activity in these models. Furthermore, minimum effective doses observed in the preclinical models and the pharmacokinetic properties of the compound support prediction of treatment regimens in humans compatible with the target patient population and disease," said Sonia Poli, head of non-clinical development at Addex.
GABA(B) activation is a clinically validated mechanism. Baclofen, a GABA(B) agonist, is widely used for its muscle relaxant properties in the control of spasticity caused by multiple sclerosis, cerebral palsy or certain injuries to the spine. Furthermore, Baclofen is a powerful analgesic agent, especially when delivered intrathecally. However, rapid induction of tolerance and dose limiting CNS-mediated side effects (e.g. sedation, hypothermia, memory impairment) prevent baclofen from being widely prescribed for pain relief despite its analgesic properties. ADX71943, an allosteric modulator with a differentiated profile, could avoid the tolerance and dose limiting side effects commonly associated with baclofen.
Addex Pharmaceuticals utilizes its unique proprietary platform technologies to discover and develop allosteric modulators for human health.