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

Abstract

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 Abeta-fiber-mediated response with the Neurometer. I.c.v. pretreatment with the alpha1-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 alpha1-adrenoceptor and the GABAB 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.