Analgesic properties of the novel compound M43068 in rat models of acute and neuropathic pain

We investigated the effects of 2-(4-hydroxybenzoyl)amino-2-methylpropionic acid (M43068), a novel analgesic agent, in rat models of acute and neuropathic pain. Oral M43068 (10-100 mg/kg) suppressed only the late phase of formalin-induced nociceptive behaviors. In the neuropathic pain model, oral M43068 (10-100 mg/kg) suppressed mechanical allodynia in the nerve-injured paw without affecting normal thresholds. On the other hand, i.v. M43068 (30 mg/kg) mainly suppressed the A beta-fiber-mediated response with the Neurometer. I.c.v. pretreatment with the alpha(1)-adrenoceptor antagonist, prazosin, or i.p. pretreatment with the gamma-aminobutyric acid (GABA)(B) receptor antagonist, saclofen, abolished the M43068-induced antinociception. However, oral M43068 (30-300 mg/kg) had no influence on blood pressure and motor function, unlike the alpha(1)-adrenoceptor and the GABA(B) receptor agonists. These data indicate that M43068 shows antinociceptive and anti-allodynic effects with reduced risks of side effects. It is suggested that the descending noradrenergic system is involved in the analgesic effects of M43068. (c) 2005 Elsevier B.V All rights reserved.