Juan Rodríguez-Silverio, María Sánchez-Mendoza, Héctor Rocha-González, Yaraset López-Lorenzo, Juan Reyes-García, Juan Huerta-Cruz and Jesús Arrieta
Background and Objective: Pain is an unpleasant sensation related to actual or potential tissue damage. The ongoing search for antinociceptive compounds owes itself to the adverse effects of current analgesics. This study aimed to evaluate the antinociceptive effect of Calein D in the rat formalin model. Materials and Methods: Antinociceptive activity was tested for Calein D (at various doses) and a reference drug (piroxicam) in the rat formalin model. To investigate whether muscarinic receptors, serotonin receptors, opioid receptors and nitric oxide (NO) participate in the antinociceptive effect found for Calein D, rats were pretreated with atropine, methiothepin, naloxone or NG-Nitro-L-Arginine Methyl Ester Hydrochloride (L-NAME), respectively. To assess the possible role of μ, δ and κ opioid receptor subtypes, animals were pretreated with the selective antagonists CTOP (a selective μ opioid receptor antagonist), SDM-25N (a selective δ opioid receptor antagonist) or nor-binaltorphimine (nor-BNI, a selective κ opioid receptor antagonist), respectively. Results: Calein D showed its maximum antinociceptive effect at 56 mg/kg (57.03±2.85%), compared to 35-60% for non-steroidal anti-inflammatory drugs (NSAIDs) in the formalin model. It exhibited significantly greater activity than piroxicam (both at 32 mg/kg; 49.21±4.76% vs. 32.24±8.73%; p<0.05). The mechanism of action of Calein D involves muscarinic receptors as well as μ and δ opioid receptors, but not serotonin receptors, κ opioid receptors or NO. Conclusion: This was the first report on the antinociceptive activity of D-calein. Muscarinic and opioid receptors are involved in its mechanism of action.
Juan Rodríguez-Silverio, María Sánchez-Mendoza, Héctor Rocha-González, Yaraset López-Lorenzo, Juan Reyes-García, Juan Huerta-Cruz and Jesús Arrieta, 2024. Evaluation of the Antinociceptive Activity of Calein D and Exploration of the Possible Mechanism of Action. International Journal of Pharmacology, 20: 1501-1511.