The antinociceptive activity of harmicine on chemical-induced neurogenic and inflammatory pain models in mice

Harmicine is a β-carboline alkaloid isolated and identified as a major active compound present in many plant species and marine invertebrates. This alkaloid exhibits a wide spectrum of pharmacological activities, including antispasmodic, antipyretic, and anticancer properties. This report described the antinociceptive properties of harmicine by means of chemical experimental models in order to evaluate the use for pain relief. The results demonstrating the potential analgesic properties of harmicine administered intraperitoneally were shown with the writhing test, reducing writhes around 60% (1mg/kg), and in the formalin test, where harmicine was more effective toward neurogenic (reducing reaction time around 60%, 1mg/kg) than inflammatory (68% reduction, 10mg/kg) pain responses. Furthermore, these effects may operate via vanilloid receptors as revealed by the capsaicin test (41% reduction, with 3mg/kg), as well as via peripheral glutamate receptors as shown by the glutamate test (50% reduction, with 1mg/kg). Moreover, the opioid antagonist naloxone hydrochloride did not interfere in the antinociceptive properties of harmicine in the writhing test, revealing that this effect may not have a relationship with the opioid systems. Concluding, this report highlights harmicine as a new candidate to be used as analgesic in the future. Therefore, further studies are being undertaken in order to understand the exact mechanisms involved with the antinociceptive properties of harmicine. ► We examined the potential use of harmicine for pain relief. ► We tested using chemical assays of pain ► Harmicine demonstrated effectiveness against neurogenic pain stimuli. ► The compound seems to act peripherally via vanilloid and glutamatergic systems. ► Harmicine seems not to act via opioid system in the writhing test.