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Antinociceptive action of isolated mitragynine from Mitragyna Speciosa through activation of opioid receptor system.

Shamima AR, Fakurazi S, Hidayat MT, Hairuszah I, Moklas MA, Arulselvan P - Int J Mol Sci (2012)

Bottom Line: Previous findings have shown that mitragynine (MG), a major indole alkaloid found in Mitragyna speciosa (MS) can exert its antinociceptive effects through the opioids system.Naloxonazine did inhibit the effect of MG, but it was not statistically significant.These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmacy, Cyberjaya University College of Medical Sciences, 63000 Cyberjaya, Selangor, Malaysia; E-Mail: alfaqirah_msc@yahoo.com.

ABSTRACT
Cannabinoids and opioids systems share numerous pharmacological properties and antinociception is one of them. Previous findings have shown that mitragynine (MG), a major indole alkaloid found in Mitragyna speciosa (MS) can exert its antinociceptive effects through the opioids system. In the present study, the action of MG was investigated as the antinociceptive agent acting on Cannabinoid receptor type 1 (CB1) and effects on the opioids receptor. The latency time was recorded until the mice showed pain responses such as shaking, licking or jumping and the duration of latency was measured for 2 h at every 15 min interval by hot plate analysis. To investigate the beneficial effects of MG as antinociceptive agent, it was administered intraperitoneally 15 min prior to pain induction with a single dosage (3, 10, 15, 30, and 35 mg/kg b.wt). In this investigation, 35 mg/kg of MG showed significant increase in the latency time and this dosage was used in the antagonist receptor study. The treated groups were administered with AM251 (cannabinoid receptor-1 antagonist), naloxone (non-selective opioid antagonist), naltrindole (δ-opioid antagonist) naloxonazine (μ(1)-receptor antagonist) and norbinaltorpimine (κ-opioid antagonist) respectively, prior to administration of MG (35 mg/kg). The results showed that the antinociceptive effect of MG was not antagonized by AM251; naloxone and naltrindole were effectively blocked; and norbinaltorpimine partially blocked the antinociceptive effect of MG. Naloxonazine did inhibit the effect of MG, but it was not statistically significant. These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.

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Related in: MedlinePlus

The effects of mitragynine (3 mg/kg, 10 mg/kg, 15 mg/kg, 30 mg/kg and 35 mg/kg), morphine and control on latency time in hot-plate test (HPT) for various time intervals. Mitragynine was administered 15 min before the HPT intraperitoneally (i.p). Each column represents the mean ± SEM of latency time (s) for group of eight animals in each group. Values are statistically significant at p < 0.05. a 35 mg/kg b.wt of MG treated groups were compared to normal saline (vehicle control) group; b 35 mg/kg b.wt of MG treated groups were compared to 3 mg/kg b.wt morphine group.
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f4-ijms-13-11427: The effects of mitragynine (3 mg/kg, 10 mg/kg, 15 mg/kg, 30 mg/kg and 35 mg/kg), morphine and control on latency time in hot-plate test (HPT) for various time intervals. Mitragynine was administered 15 min before the HPT intraperitoneally (i.p). Each column represents the mean ± SEM of latency time (s) for group of eight animals in each group. Values are statistically significant at p < 0.05. a 35 mg/kg b.wt of MG treated groups were compared to normal saline (vehicle control) group; b 35 mg/kg b.wt of MG treated groups were compared to 3 mg/kg b.wt morphine group.

Mentions: MG (3–35mg/kg, i.p) was found to induce dose-dependent antinociceptive response in the hot plate test. In Figure 4, the administration of 15 mg/kg of MG increased the latency period. The dose dependent effect was observed at all-time points. The best antinociceptive effect was observed with concentration 35 mg/kg of MG that resulted in a significant increase (p < 0.05) in latency time when compared to vehicle and morphine groups. Dose-response curve was generated from each dosage to determine the effective dose 50 (ED50) of MG (Figure 5). MG dose ranging from 3 to 60 mg/kg b.wt was tested for antinociceptive effects in experimental system. Findings from the dose response curve, mitragynine was showed significant antinociceptive effect and this effect of MG was showed in dose dependent manner. However, the antinociceptive effect of MG was marginally reduced at 40 mg/kg and 60 mg/kg (data not shown).


Antinociceptive action of isolated mitragynine from Mitragyna Speciosa through activation of opioid receptor system.

Shamima AR, Fakurazi S, Hidayat MT, Hairuszah I, Moklas MA, Arulselvan P - Int J Mol Sci (2012)

The effects of mitragynine (3 mg/kg, 10 mg/kg, 15 mg/kg, 30 mg/kg and 35 mg/kg), morphine and control on latency time in hot-plate test (HPT) for various time intervals. Mitragynine was administered 15 min before the HPT intraperitoneally (i.p). Each column represents the mean ± SEM of latency time (s) for group of eight animals in each group. Values are statistically significant at p < 0.05. a 35 mg/kg b.wt of MG treated groups were compared to normal saline (vehicle control) group; b 35 mg/kg b.wt of MG treated groups were compared to 3 mg/kg b.wt morphine group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472755&req=5

f4-ijms-13-11427: The effects of mitragynine (3 mg/kg, 10 mg/kg, 15 mg/kg, 30 mg/kg and 35 mg/kg), morphine and control on latency time in hot-plate test (HPT) for various time intervals. Mitragynine was administered 15 min before the HPT intraperitoneally (i.p). Each column represents the mean ± SEM of latency time (s) for group of eight animals in each group. Values are statistically significant at p < 0.05. a 35 mg/kg b.wt of MG treated groups were compared to normal saline (vehicle control) group; b 35 mg/kg b.wt of MG treated groups were compared to 3 mg/kg b.wt morphine group.
Mentions: MG (3–35mg/kg, i.p) was found to induce dose-dependent antinociceptive response in the hot plate test. In Figure 4, the administration of 15 mg/kg of MG increased the latency period. The dose dependent effect was observed at all-time points. The best antinociceptive effect was observed with concentration 35 mg/kg of MG that resulted in a significant increase (p < 0.05) in latency time when compared to vehicle and morphine groups. Dose-response curve was generated from each dosage to determine the effective dose 50 (ED50) of MG (Figure 5). MG dose ranging from 3 to 60 mg/kg b.wt was tested for antinociceptive effects in experimental system. Findings from the dose response curve, mitragynine was showed significant antinociceptive effect and this effect of MG was showed in dose dependent manner. However, the antinociceptive effect of MG was marginally reduced at 40 mg/kg and 60 mg/kg (data not shown).

Bottom Line: Previous findings have shown that mitragynine (MG), a major indole alkaloid found in Mitragyna speciosa (MS) can exert its antinociceptive effects through the opioids system.Naloxonazine did inhibit the effect of MG, but it was not statistically significant.These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmacy, Cyberjaya University College of Medical Sciences, 63000 Cyberjaya, Selangor, Malaysia; E-Mail: alfaqirah_msc@yahoo.com.

ABSTRACT
Cannabinoids and opioids systems share numerous pharmacological properties and antinociception is one of them. Previous findings have shown that mitragynine (MG), a major indole alkaloid found in Mitragyna speciosa (MS) can exert its antinociceptive effects through the opioids system. In the present study, the action of MG was investigated as the antinociceptive agent acting on Cannabinoid receptor type 1 (CB1) and effects on the opioids receptor. The latency time was recorded until the mice showed pain responses such as shaking, licking or jumping and the duration of latency was measured for 2 h at every 15 min interval by hot plate analysis. To investigate the beneficial effects of MG as antinociceptive agent, it was administered intraperitoneally 15 min prior to pain induction with a single dosage (3, 10, 15, 30, and 35 mg/kg b.wt). In this investigation, 35 mg/kg of MG showed significant increase in the latency time and this dosage was used in the antagonist receptor study. The treated groups were administered with AM251 (cannabinoid receptor-1 antagonist), naloxone (non-selective opioid antagonist), naltrindole (δ-opioid antagonist) naloxonazine (μ(1)-receptor antagonist) and norbinaltorpimine (κ-opioid antagonist) respectively, prior to administration of MG (35 mg/kg). The results showed that the antinociceptive effect of MG was not antagonized by AM251; naloxone and naltrindole were effectively blocked; and norbinaltorpimine partially blocked the antinociceptive effect of MG. Naloxonazine did inhibit the effect of MG, but it was not statistically significant. These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.

Show MeSH
Related in: MedlinePlus