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 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.
Akada
Yasushige
Y
Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd. 722 Jimba-aza-Uenohara, Gotemba, Shizuoka 412-8524, Japan. yakada@mochida.co.jp
Mori
Reiko
R
Kato
Yutaka
Y
Yamasaki
Fumiaki
F
Mochizuki
Hidenori
H
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005557:Formaldehyde; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D006930:Hyperalgesia / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D017288:Pain Threshold / Q000187:drug effects; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000601:surgery; D020426:Sciatic Neuropathy / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects; D013997:Time Factors; D014110:Touch
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D011422:Propionates; D005557:Formaldehyde; D001418:Baclofen; C080629:saclofen; D011224:Prazosin