Filicene obtained from Adiantum cuneatum interacts with the cholinergic, dopaminergic, glutamatergic, GABAergic, and tachykinergic systems to exert antinociceptive effect in mice.
In the present study, we describe the antinociceptive effect of filicene, a triterpene isolated from Adiantum cuneatum (Adiantaceae) leaves, in several models of pain in mice. When evaluated against acetic acid-induced abdominal constrictions, filicene (10, 30 and 60 mg/kg, i.p.) produced dose-related inhibition of the number of constrictions, being several times more potent [ID(50)=9.17 (6.27-13.18) mg/kg] than acetaminophen [ID(50)=18.8 (15.7-22.6) mg/kg], diclofenac [ID(50)=12.1(9.40-15.6) mg/kg] and acetylsalicylic acid [ID(50)=24.0(13.1-43.8) mg/kg] in the same doses as those used for the standard drugs. Filicene also produced dose-related inhibition of the pain caused by capsaicin and glutamate, with mean ID(50) values of 11.7 (8.51-16.0) mg/kg and <10 mg/kg, respectively. Its antinociceptive action was significantly reversed by atropine, haloperidol, GABA(A) and GABA(B) antagonists (bicuculline and phaclofen, respectively), but was not affected by L-arginine-nitric oxide, serotonin, adrenergic and the opioid systems. Together, these results indicate that the mechanisms involved in its action are not completely understood, but seem to involve interaction with the cholinergic, dopaminergic, glutamatergic, GABAergic and tachykinergic systems.
Programa de Mestrado em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), 88302-202, Itajaí, SC, Brazil.
M M
MM
De Souza
M A
MA
Pereira
J V
JV
Ardenghi
T C
TC
Mora
L F
LF
Bresciani
R A
RA
Yunes
F
F
Delle Monache
V
V
Cechinel-Filho
D019342:Acetic Acid / Q000633:toxicity; D035681:Adiantum / Q000737:chemistry*; D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D008517:Phytotherapy; D010946:Plants, Medicinal / Q000737:chemistry; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D018039:Receptors, Tachykinin / Q000187:drug effects / Q000502:physiology; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D000700:Analgesics; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D018079:Receptors, GABA; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D014315:Triterpenes; C542911:filicene; C069474:glutamine receptor; D018698:Glutamic Acid; D019342:Acetic Acid; D002211:Capsaicin