title: Antinociceptive profiles and mechanisms of orally administered coumarin in mice.
abstract: In the present study, the antinociceptive profiles of coumarin were examined in ICR mice. Coumarin administered orally (from 1 to 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Duration of antinociceptive action of coumarin maintained at least for 60 min. But, the cumulative response time of nociceptive behaviors induced by a subcutaneous (s.c.) formalin injection, intrathecal (i.t.) substance P (0.7 µg) or glutamate (20 µg) injection was not affected by coumarin. In addition, intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration with coumarin (10-40 µg) attenuated acetic acid-induced writhing response in a dose dependent manner. Intraperitoneal (i.p.) pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by coumarin in the writhing test. Furthermore, i.c.v. or i.t. pretreatment with naloxone (5 µg) reversed the decreased acetic acid-induced writhing response. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an α2-adrenergic receptor antagonist) did not affect antinociception induced by coumarin in the writhing test. Our results suggest that coumarin exerts a selective antinociceptive property in the acetic acid-induced visceral-derived pain model. Furthermore, the antinociceptive effect of coumarin may be mediated by activation of central opioid receptors, but not serotonergic and adrenergic receptors.
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Yun-Beom
authors.initials: YB
authors.lastname: Sim
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Kang
authors.forename: Sung-Su
authors.initials: SS
authors.lastname: Kim
authors.forename: Chea-Ha
authors.initials: CH
authors.lastname: Kim
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Su-Min
authors.initials: SM
authors.lastname: Lim
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
mesh_terms: D019342:Acetic Acid; D000284:Administration, Oral; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003374:Coumarins / Q000627:therapeutic use*; D005557:Formaldehyde; D018698:Glutamic Acid; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011957:Receptors, Opioid / Q000502:physiology; D013373:Substance P
chemical_list: D000700:Analgesics; D003374:Coumarins; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D005557:Formaldehyde; D013373:Substance P; D009270:Naloxone; D018698:Glutamic Acid; C030123:coumarin; D019342:Acetic Acid