Effects of isopulegol in acute nociception in mice: Possible involvement of muscarinic receptors, opioid system and l-arginine/NO/cGMP pathway.

Abstract

Previous studies have shown that isopulegol has anxiolytic, anticonvulsant, gastro-protective and antioxidant activities in rodents, but until now there are no studies showing activity of isopulegol in animal models of nociception and inflammation. The objective of this study was to evaluate the antinociceptive effect of isopulegol and to propose possible mechanisms involved in its effects observed in mice. Groups of male and female Swiss mice (20-35 g, n = 5-8) were used in this test under the authorization of Ethics Committee on Animal Experimentation (CEEA/UFPI N° 82/2014). In order to evaluate the antinociceptive activity of isopulegol, nociception was induced using formalin test, capsaicin and glutamate in hind paw licking model, followed by the investigation of the involvement of opioid mechanisms, K + ATP channels, muscarinic, L arginine-nitric oxide and cGMP. The oral administration of isopulegol showed antinociceptive effect in both phases of the formalin test at doses from 0.78 to 25 mg/kg (first phase) and 1.56-25 mg/kg (second phase) and also produced significant results before capsaicin test at doses from 1.56 to 12.5 mg/kg and glutamate test at doses from 3.12 to 6.25 mg/kg with a dose-dependent effect. The antinociception activity of isopulegol was inhibited in the presence of naloxone (2 mg / kg, ip), glibenclamide (3 mg/kg, ip), atropine (1 mg/kg, ip), l-arginine (600 mg/kg, ip) and methylene blue (20 mg/kg, ip). The results suggested that acute antinociceptive action of opioid isopulegol seems to be related to the K + ATP channels system, through the involvement of muscarinic receptors, inhibiting nitric oxide and cGMP.

• Authors: Deyna Francélia Andrade Próspero, Antonio Carlos Reis Filho, Celyane Alves Piauilino, Everton Moraes Lopes, Damião Pergentino de Sousa, Fernanda Regina de Castro Almeida
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 293 Pg. 55-60 (Sep 25 2018) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 30053451 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• Analgesics
• Cyclohexane Monoterpenes
• Receptors, Muscarinic
• Receptors, Opioid
• Terpenes
• Formaldehyde
• Nitric Oxide
• Glutamic Acid
• isopulegol
• Arginine
• Cyclic GMP
• Capsaicin

Topics

• Acute Disease
• Administration, Oral
• Analgesics (pharmacology)
• Animals
• Arginine (metabolism)
• Behavior, Animal (drug effects)
• Capsaicin (pharmacology)
• Cyclic GMP (metabolism)
• Cyclohexane Monoterpenes
• Female
• Formaldehyde (pharmacology)
• Glutamic Acid (pharmacology)
• Male
• Mice
• Nitric Oxide (metabolism, therapeutic use)
• Pain (chemically induced, drug therapy)
• Receptors, Muscarinic (metabolism)
• Receptors, Opioid (metabolism)
• Signal Transduction (drug effects)
• Terpenes (chemistry, pharmacology, therapeutic use)