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Published on: July 29, 2014
Opioid system mediated anti-nociceptive effect of agomelatine in mice
Merve Kasap1, Özgür Devrim Can2
1Anadolu University Graduate School of Health Sciences, Department of Pharmacology, 26470 Eskişehir, Turkey.
Aims:
This study was planned to examine the antinociceptive efficacy of agomelatine against acute mechanical, thermal, and chemical nociceptive stimuli, as well as to determine the opioid receptor subtypes mediating these effects.
Main Methods:
Tail-clip, hot-plate, and acetic acid-induced writhing tests were performed to evaluate anti-nociceptive effect. Besides, possible effect of agomelatine on the motor coordination of animals was assessed with a Rota-rod test.
Key Findings:
Agomelatine (40mg/kg and 60mg/kg) significantly prolonged the reaction time of mice in both the tail-clip and hot-plate tests, suggesting the antinociceptive activity is related to both spinal and supraspinal mechanisms. This drug also reduced the number of writhing behaviors indicating the presence of a peripherally mediated antinociceptive effect. Rota-rod testing displayed no notable effect on the motor activity of the animal supporting the conclusion that the observed antinociceptive effect is specific. The agomelatine-induced antinociceptive activity abrogated following pretreatment with naloxone (a non-selective opioid receptor antagonist, 5.48mg/kg, i.p.), which suggested the participation of opioid mechanisms to the antinociception. The possible contribution of μ, δ and ҡ subtypes of opioid receptors to the anti-nociceptive effect were evaluated using naloxonazine (7mg/kg, s.c.), naltrindole (0.99mg/kg, i.p.), and nor-binaltorphimine (1.03mg/kg, i.p.), respectively. Pretreatments using these antagonists abolished the antinociceptive activity of agomelatine in all of the nociceptive test paradigms used, which pointed out that μ, δ, and ҡ opioid receptors participated to the action of agomelatine on pain.
Significance:
These results demonstrated the therapeutic potential of agomelatine in the treatment of pain disorders.
Insights
Agomelatine exhibits significant antinociceptive effects against various pain stimuli by engaging mu, delta, and kappa opioid receptors. This study highlights its potential for treating pain disorders.
Area of Science:
- Pharmacology
- Neuroscience
- Pain Research
Background:
- Pain management remains a significant clinical challenge.
- Novel therapeutic agents targeting diverse pain pathways are needed.
Purpose of the Study:
- To evaluate the antinociceptive efficacy of agomelatine.
- To identify the specific opioid receptor subtypes involved in agomelatine's action.
Main Methods:
- Utilized tail-clip, hot-plate, and acetic acid-induced writhing tests to assess antinociception.
- Employed Rota-rod test to evaluate motor coordination.
- Investigated opioid receptor involvement using specific antagonists: naloxone, naloxonazine, naltrindole, and nor-binaltorphimine.
Main Results:
- Agomelatine demonstrated significant antinociceptive activity across mechanical, thermal, and chemical pain models.
- The effects were mediated through spinal, supraspinal, and peripheral mechanisms.
- Agomelatine's antinociceptive action was abolished by opioid receptor antagonists, indicating involvement of mu, delta, and kappa opioid receptors.
- No significant impact on motor coordination was observed, suggesting specificity.
Conclusions:
- Agomelatine possesses broad-spectrum antinociceptive properties.
- Its efficacy is linked to the modulation of mu, delta, and kappa opioid receptors.
- Agomelatine shows therapeutic promise for pain disorder treatment.
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