Role of nitric oxide/cyclic GMP/K(+) channel pathways in the antinociceptive effect caused by 2,3-bis(mesitylseleno)propenol.
The present study examined the antinociceptive effects induced by 2,3-bis(mesitylseleno)propenol, a bis-selenide alkene derivate, given orally, in chemical models of pain in rats and mice. Selenide administered orally (p.o.) into the rats caused antinociception against the first and second phases of the formalin test, with mean ID(50) values of 28.17 and 39.68 mg/kg, respectively. The antinociceptive effect caused by selenide (50 mg/kg, p.o.) on the formalin test was reversed by pretreatment with N(G)-L-nitro-arginine methyl ester (L-NAME, a nitric oxide (NO) synthase inhibitor), methylene blue (a non-specific NO/guanylyl cyclase inhibitor) and glibenclamide (an ATP-sensitive K(+) channel inhibitor), but not by atropine (a muscarinic antagonist). Given orally selenide in mice produced an inhibition of glutamate-, histamine- and compound 48/80-induced nociception with mean ID(50) values of 27.58, 36.18 and 44.53 mg/kg, respectively. Moreover, oral treatment with selenide in mice decreased licking -- induced by serotonin (mean ID(50) value of >50 mg/kg). The data show that selenide exerts pronounced systemic antinociception in chemical (formalin, glutamate, histamine, compound 48/80 and serotonin-induced pain) models of nociception. Taken together, these results suggest that the antinociceptive effect of selenide on the formalin test involves the participation of nitric oxide/cyclic GMP/K(+) channel pathways in rats.
Jesse
Cristiano Ricardo
CR
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Savegnago
Lucielli
L
Nogueira
Cristina Wayne
CW
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D018698:Glutamic Acid; D005905:Glyburide; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology* / Q000517:prevention & control; D010147:Pain Measurement; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D003189:p-Methoxy-N-methylphenethylamine
C526515:2,3-bis(mesitylseleno)propenol; D000700:Analgesics; D016566:Organoselenium Compounds; D015221:Potassium Channels; D005557:Formaldehyde; D009569:Nitric Oxide; D012701:Serotonin; D018698:Glutamic Acid; D003189:p-Methoxy-N-methylphenethylamine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester