title: Antinociceptive properties of selective MT(2) melatonin receptor partial agonists.
abstract: Melatonin is a neurohormone involved in the regulation of both acute and chronic pain whose mechanism is still not completely understood. We have recently demonstrated that selective MT2 melatonin receptor partial agonists have antiallodynic properties in animal models of chronic neuropathic pain by modulating ON/OFF cells of the descending antinociceptive system. Here, we examined the antinociceptive properties of the selective MT2 melatonin receptor partial agonists N-{2-[(3-methoxyphenyl)phenylamino]ethyl}acetamide (UCM765) and N-{2-[(3-bromophenyl)-(4-fluorophenyl)amino]ethyl}acetamide (UCM924) in two animal models of acute and inflammatory pain: the hot-plate and formalin tests. UCM765 and UCM924 (5-40 mg/kg, s.c.) dose-dependently increased the temperature of the first hind paw lick in the hot-plate test, and decreased the total time spent licking the injected hind paw in the formalin test. Antinociceptive effects of UCM765 and UCM924 were maximal at the dose of 20mg/kg. At this dose, the effects of UCM765 and UCM924 were similar to those produced by 200 mg/kg acetaminophen in the hot-plate test, and by 3 mg/kg ketorolac or 150 mg/kg MLT in the formalin test. Notably, antinociceptive effects of the two MT2 partial agonists were blocked by the pre-treatment with the MT2 antagonist 4-phenyl-2-propionamidotetralin (4P-PDOT, 10 mg/kg) in both paradigms. These results demonstrate the antinociceptive properties of UCM765 and UCM924 in acute and inflammatory pain models and corroborate the concept that MT2 melatonin receptor may be a novel target for analgesic drug development.
authors.affiliation: Neurobiological Psychiatry Unit, Dept. Psychiatry, McGill University, Montreal, Canada; University Veracruzana, Xalapa, Veracruz, México.
authors.forename: Martha
authors.initials: M
authors.lastname: López-Canul
authors.affiliation: Neurobiological Psychiatry Unit, Dept. Psychiatry, McGill University, Montreal, Canada.
authors.forename: Stefano
authors.initials: S
authors.lastname: Comai
authors.affiliation: Neurobiological Psychiatry Unit, Dept. Psychiatry, McGill University, Montreal, Canada.
authors.forename: Sergio
authors.initials: S
authors.lastname: Domínguez-López
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Cinvestav, Sede Sur, México, D.F., México.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
authors.affiliation: Neurobiological Psychiatry Unit, Dept. Psychiatry, McGill University, Montreal, Canada. Electronic address: gabriella.gobbi@mcgill.ca.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gobbi
mesh_terms: D000081:Acetamides / Q000378:metabolism / Q000494:pharmacology*; D000082:Acetaminophen / Q000494:pharmacology; D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology*; D000814:Aniline Compounds / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D054333:Drug Partial Agonism; D005557:Formaldehyde; D020910:Ketorolac / Q000494:pharmacology; D008297:Male; D059225:Nociception / Q000187:drug effects*; D059226:Nociceptive Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D011485:Protein Binding; D017208:Rats, Wistar; D044123:Receptor, Melatonin, MT2 / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors
chemical_list: C114459:4-phenyl-2-propionamidotetraline; D000081:Acetamides; D000700:Analgesics; D000814:Aniline Compounds; C545681:N-(2-((3-bromophenyl)-(4-fluorophenyl)amino)ethyl)acetamide; C545680:N-(2-((3-methoxyphenyl)phenylamino)ethyl)acetamide; D044123:Receptor, Melatonin, MT2; D013764:Tetrahydronaphthalenes; D005557:Formaldehyde; D000082:Acetaminophen; D020910:Ketorolac
keywords: Acute pain; Antinociception; Formalin test; Hot-plate test; MT(2) receptor partial agonists; Melatonin