1.Evaluation of the antinociceptive effects of a selection of triazine derivatives in mice
Valiollah HAJHASHEMI ; Ghadamali KHODARAHMI ; Parvin ASADI ; Hamed RAJABI
The Korean Journal of Pain 2022;35(4):440-446
Background:
The authors showed in a previous study that some novel triazine derivatives had an anti-inflammatory effect. The present study was designed to evaluate the antinociceptive effect of five out of nine compounds including two vanillintriazine (5c and 5d) and three phenylpyrazole-triazine (10a, 10b, 10e) derivatives which showed the best anti-inflammatory effect.
Methods:
Male Swiss mice (25–30 g) were used. To assess the antinociceptiveeffect, acetic acid-writhing, formalin, and hot plate tests were used after intraperitoneal injection of each compound.
Results:
All compounds significantly (P < 0.001) reduced acetic acid-induced writhing at tested doses (50, 100, and 200 mg/kg). Also, the percent inhibition of writhing in the acetic acid test showed that at the maximum tested dose of these compounds (200 mg/kg), the order of potencies is as follows: 10b > 10a > 10e > 5d > 5c. In the formalin test, compounds 5d, 10a, and 10e showed an antinociceptive effect in the acute phase and all compounds were effective in the chronic phase. In the hot plate test, compounds 5c, 5d, and 10a demonstrated an antinociceptive effect.
Conclusions
The results clearly showed that both vanillin-triazine and phenylpyrazole-triazine derivatives had an antinociceptive effect. Also, some compounds which showed activity in the early phase of formalin test as well as in the hot plate test could control acute pain in addition to chronic or inflammatory pain.
2.Anti-inflammatory and antinociceptive effects of sitagliptin in animal models and possible mechanisms involved in the antinociceptive activity
Valiollah HAJHASHEMI ; Hossein SADEGHI ; Fatemeh Karimi MADAB
The Korean Journal of Pain 2024;37(1):26-33
Background:
Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity.
Methods:
Male Swiss mice (25–30 g) and male Wistar rats (180–220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/K ATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg).
Results:
Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly (P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT 2 ) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect.
Conclusions
NO/cGMP/K ATP , 5HT3 and D2 pathways play an important role in the antinociceptive effect of sitagliptin.Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.
3.Anti-inflammatory and antinociceptive effects of sitagliptin in animal models and possible mechanisms involved in the antinociceptive activity
Valiollah HAJHASHEMI ; Hossein SADEGHI ; Fatemeh Karimi MADAB
The Korean Journal of Pain 2024;37(1):26-33
Background:
Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity.
Methods:
Male Swiss mice (25–30 g) and male Wistar rats (180–220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/K ATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg).
Results:
Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly (P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT 2 ) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect.
Conclusions
NO/cGMP/K ATP , 5HT3 and D2 pathways play an important role in the antinociceptive effect of sitagliptin.Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.
4.Anti-inflammatory and antinociceptive effects of sitagliptin in animal models and possible mechanisms involved in the antinociceptive activity
Valiollah HAJHASHEMI ; Hossein SADEGHI ; Fatemeh Karimi MADAB
The Korean Journal of Pain 2024;37(1):26-33
Background:
Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity.
Methods:
Male Swiss mice (25–30 g) and male Wistar rats (180–220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/K ATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg).
Results:
Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly (P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT 2 ) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect.
Conclusions
NO/cGMP/K ATP , 5HT3 and D2 pathways play an important role in the antinociceptive effect of sitagliptin.Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.