Eugenol and its symmetrical dimer bis-eugenol as well as the bromo-bis-eugenol derivative(±)-2,2’-dihydroxy-3,3’-dimethoxy-5,5’-diallyl-6,6’-dibromo-1,1’-biphenyl [(±)-1] and both its enantiomers, (aR)-(+)-2,2’-dihydroxy-3,3’-dimethoxy-5,5’-diallyl-6,6’-dibromo-1,1’-biphenyl [(aR)-(+)-1] and (aS)-(-)-2,2’-dihydroxy-3,3’-dimethoxy-5,5’-diallyl-6,6’-dibromo-1,1’-biphenyl [(aS)-(-)-1], previously synthesized, were tested in the carrageenin-induced paw oedema in the rat and in the writhing induced by acetic acid in the mouse. Experimental data indicate that acute systemic administration of assayed compounds, at the dose of 50 mg/kg, did not inhibit oedema development whereas all caused a significant effect in visceral pain as revealed by the reduction of the number of writhing responses. At the dose tested, no significant differences were observed between the racemate form (±)-1 and the (aR)-(+)-1 and (aS)-(-)-1 enantiomers and between eugenol and bis-eugenol. In addition, the antinociception of the racemate (±)-1 and its respective enantiomers (aR)-(+)- 1 and (aS)-(-)-1 was not mediated by the opioid receptors since opioid receptor antagonist, naloxone did not reverse bromo-bis-eugenol derivatives-produced antinociception. Moreover, to further characterise the antinociceptive profile of bromo-bis-eugenol derivatives we have also examined the effects on carrageenin-induced thermal hyperalgesia in rat paw. All bromo-bis-eugenol derivatives did not increase the paw withdrawal latency on both paws, the site of carrageenin injection and the contralateral side. In conclusion, eugenol, bis-eugenol and bromo-bis-eugenol derivatives produced a reduction of visceral pain but had no effect on inflammation. Moreover, bromo-bis-eugenol derivatives failed in reducing the inflammatory pain showing also a lack of antinociceptive effect on thermal pain. These interesting findings provide some information that will be useful for further studying and development of these compounds for clinical use.
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