Assessment of mechanisms involved in antinociception caused by myrsinoic acid B.
Myrsinoic acid B (AMB) is a prenylated-benzoic acid derivative isolated from the Rapanea genus. Recent studies suggest that AMB has antihyperalgesic and antinociceptive properties in different animal models. The present study was designed to investigate the mechanisms involved in antinociception elicited by AMB (60 mg/kg) when administered by intraperitonial route (i.p.) in mice. The antinociceptive response of the compound was characterized by a reduction in contractions of the abdominal muscle, together with stretching of the hind limbs in response to i.p. injection of acetic acid (0.6%, 0.45 ml/mouse). The antinociception caused by AMB in the acetic acid test was significantly attenuated by i.p. treatment of mice with nitric oxide precursor, (L-arginine, 600 mg/kg), alpha2 and alpha1-adrenoceptor antagonists (yohimbine, 0.2 mg/kg/prazosin, 0.2 mg/kg), p-chlorophenylalanine (PCPA) an inhibitor of serotonin synthesis (100 mg/kg), 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN 190), a 5-HT1(A) selective receptor antagonist (0.5 mg/kg) and a non-selective cholinergic antagonist (atropine, 10 mg/kg). Its action was also modulated by the adrenal-gland hormones. In contrast, antinociception was not affected by naloxone (non-selective opioid receptor antagonist, 1.0 mg/kg), phaclofen (2.0 mg/kg) and bicuculline (1.0 mg/kg) GABA(B) and GABA(A) receptor antagonists, respectively, ondansetron (0.3 mg/kg) and ketaserin (1.0 mg/kg), (5-HT3 and 5-HT2 receptors, respectively) and haloperidol (0.2 mg/kg), a non-selective dopaminergic receptor. The antinociceptive effects are not related to muscle-relaxant or sedative action. These results indicate that AMB produces antinociception through mechanisms that involve interaction with L-arginine-nitric oxide, the serotonergic and cholinergic systems, as well as interaction with the alpha-adrenoceptors.
Hess
Sarai
S
Centro de Ciências da Saúde/Programa de Mestrado em Ciências Farmacêuticas, Universidade do Vale do Itajaí, Rua Uruguai, 458, CEP-88302.202 Itajaí-SC, Brazil.
Padoani
Cristina
C
Scorteganha
Laiana Carla
LC
Holzmann
Iandra
I
Malheiros
Angela
A
Yunes
Rosendo Augusto
RA
Delle Monache
Franco
F
de Souza
Márcia Maria
MM
D000475:Alkenes / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D024301:Plant Bark / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D029623:Primulaceae; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000475:Alkenes; D001572:Benzofurans; D010936:Plant Extracts; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; C468150:myrsinoic acid B; D009569:Nitric Oxide