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  • Title: Mechanisms involved in the antinociceptive and anti-inflammatory effects of bis selenide in mice.
    Author: Jesse CR, Savegnago L, Nogueira CW.
    Journal: J Pharm Pharmacol; 2009 May; 61(5):623-30. PubMed ID: 19406001.
    Abstract:
    OBJECTIVES: The present study examined the mechanisms involved in the antinociceptive effects of bis selenide [(Z)-2,3-bis(4-chlorophenylselanyl)prop-2-en-1-ol]. METHODS: The effects of oral bis selenide were tested against licking behaviour and oedema in mice induced by formalin, serotonin, histamine, glutamate, phorbol 12-myristate 13-acetate (PMA), 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) and prostaglandin E2. The effects of a variety of receptor antagonists on the antinociceptive activity were tested to determine the likely mechanism of action of bis selenide. KEY FINDINGS: Bis selenide caused antinociception on the first and second phases of the formalin test, with mean ID50 values of 34.21 (29.66-39.45) and 15.86 (12.17-20.67) mg/kg and maximal inhibition of 65+/-3% and 90+/-1%, respectively. At 50 mg/kg bis selenide significantly inhibited (31+/-2%) paw oedema induced by intraplantar injection of formalin. At 25 mg/kg given 5 min after the formalin injection, bis selenide caused a significant inhibition (42+/-5%) in the second phase of the formalin test, whereas the prophylactic treatment caused more intense inhibition (64+/-3%). Oral administration of bis selenide reduced licking and paw oedema induced by serotonin, histamine, glutamate, PGE2, PMA and 8-BrcAMP. The antinociceptive effect of bis selenide (25 mg/kg, p.o.) on the formalin test was reversed by i.p. administration of p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis), ketanserin (a selective 5-HT2A receptor antagonist), ondansetron (a 5-HT3 receptor antagonist) and ranitidine (a histamine H2-receptor antagonist). CONCLUSIONS: Glutamatergic, prostaglandin E2, serotonergic (5-HT2A and 5-HT3) and histamine H2 receptors are involved in the antinociceptive effects of bis selenide in mice. The interaction of bis selenide with protein kinase C and A signalling pathways was also demonstrated.
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