Further analysis of the antinociceptive action caused by p-methoxyl-diphenyl diselenide in mice

The objective of this study was to extend our previous findings by investigating in greater detail the mechanisms that might be involved in the antinociceptive action of p-methoxyl-diphenyl diselenide, (MeOPhSe)2, in mice. The pretreatment with nitric oxide precursor, l-arginine (600 mg/kg, intraperitoneal, i.p.), reversed antinociception caused by (MeOPhSe)2 (10 mg/kg, p.o.) or NG-nitro-l-arginine (l-NOARG, 75 mg/kg, i.p.) in the glutamate test. Ondansetron (0.5 mg/kg, i.p., a 5-HT3 receptor antagonist) and SCH23390 (0.05 mg/kg, i.p.., a D1 receptor antagonist) blocked the antinociceptive effect caused by (MeOPhSe)2. Conversely, pindolol (1 mg/kg, i.p., a 5-HT1A/1B receptor/β adrenoceptor antagonist), WAY 100635 (0.7 mg/kg, i.p., a selective 5-HT1A receptor antagonist), ketanserin (0.3 mg/kg, i.p., a selective 5-HT2A receptor antagonist), prazosin (0.15 mg/kg, i.p., an α1-adrenoreceptor antagonist), yohimbine (1.0 mg/kg, i.p., an α2-adrenoreceptor antagonist), sulpiride (5 mg/kg, i.p., a D2 receptor antagonist), naloxone (1 mg/kg, i.p., a non-selective opioid receptor antagonist) and caffeine (3 mg/kg, i.p., a non-selective adenosine receptor antagonist) did not change the antinociceptive effect of (MeOPhSe)2. (MeOPhSe)2 significantly inhibited nociception induced by intraplantar (i.pl.) injection of bradykinin (10 nmol/paw) and Des-Arg9-bradykinin (10 nmol/paw, a B1 receptor agonist). (MeOPhSe)2 significantly inhibited phorbol myristate acetate (PMA, 0.03 μg/paw, a protein kinase C (PKC) activator)-induced licking response. These results indicate that (MeOPhSe)2 produced antinociception in mice through mechanisms that involve an interaction with nitrergic system, 5-HT3 and D1 receptors. The antinociceptive effect is related to (MeOPhSe)2 ability to interact with kinin B1 and B2 receptors and PKC pathway mediated mechanisms.