Addex drug candidate effective in osteoarthritis pain model
"We believe the allosteric mechanism of ADX71943 is the key factor in the differentiated tolerability and lack of tolerance development observed in these preclinical studies. We look forward to testing this compound in humans, where we hypothesize that this product could provide not only a novel treatment for osteoarthritis pain, but also an important opioid-sparing therapy for other chronic pain indications," Addex CEO Vincent Mutel said.
The effects of ADX71943 on mechanical hyperalgesia (increased pain sensitivity) and mechanical allodynia (pain produced by a normally innocuous stimulus) were assessed in the monosodium iodoacetate (MIA) model of osteoarthritis, a model of chronic nociceptive pain. ADX71943 significantly reduced mechanical hyperalgesia and showed a trend toward reducing mechanical allodynia after both acute and sub-chronic (8 days) dosing. Statistically significant antihyperalgesic activity was observed on the first day and was maintained on day 8, despite increased pain severity.
A maximal effect of ADX71943 was already achieved with the lowest dose tested (1 mg/kg). The efficacious plasma concentration (corresponding to 1 mg/kg) was approximately 30-50 ng/mL. Importantly, no development of tolerance was observed during the eight day treatment period.
Addex reported previously that ADX71943 is orally efficacious in rodent models of inflammatory pain (formalin test and Complete Freund's Adjuvant-induced hypersensitivity) and visceral pain (acetic acid-induced writhing). ADX71943 also displays an improved tolerability profile with reduced side effects compared to baclofen.
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