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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

Effects of cannabinoid 1 receptor (CB1) antagonist AM251 on mitragynine-induced antinociception (35 mg/kg). Each column represents the mean ± SEM of latency time (s) of six animals in each group. Values are statistically significant at ap < 0.05 compared to normal saline (vehicle control) and bp < 0.05 compared to THC alone group.
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f6-ijms-13-11427: Effects of cannabinoid 1 receptor (CB1) antagonist AM251 on mitragynine-induced antinociception (35 mg/kg). Each column represents the mean ± SEM of latency time (s) of six animals in each group. Values are statistically significant at ap < 0.05 compared to normal saline (vehicle control) and bp < 0.05 compared to THC alone group.

Mentions: In order to determine which receptors were involved in antinociceptive effects of MG, we utilized receptor antagonists directed against the CB1. Receptor antagonist was administered prior to the agonist, as described in the experimental section to confirm that each antagonist blocked the respective receptor involved. As positive control, Δ-9-tetrahydrocannabinol (THC) was used. The result showed that THC increases the latency period (p < 0.05) which showed antinociceptive effects. The latency time was increased significantly, up to 60 min compared to vehicle treated groups. After 60 min, the effect decreased and was not significant when compared to the vehicle group. The MG alone group also showed a significant increase in the latency period compared to vehicle group and the significant antinociceptive effect was seen throughout the period of 120 min. The antinociceptive effect of THC was blocked by AM251. This was proved when the result showed that the latency time was significantly decreased at 30 min when compared to THC alone group (p < 0.05). However, when MG was given following prior administration of AM251, the latency time was prolonged and it was not statistically significant when compared to group with MG alone (Figure 6). These results suggested that MG did not exert the antinociceptive action through the CB1 receptor.


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)

Effects of cannabinoid 1 receptor (CB1) antagonist AM251 on mitragynine-induced antinociception (35 mg/kg). Each column represents the mean ± SEM of latency time (s) of six animals in each group. Values are statistically significant at ap < 0.05 compared to normal saline (vehicle control) and bp < 0.05 compared to THC alone group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6-ijms-13-11427: Effects of cannabinoid 1 receptor (CB1) antagonist AM251 on mitragynine-induced antinociception (35 mg/kg). Each column represents the mean ± SEM of latency time (s) of six animals in each group. Values are statistically significant at ap < 0.05 compared to normal saline (vehicle control) and bp < 0.05 compared to THC alone group.
Mentions: In order to determine which receptors were involved in antinociceptive effects of MG, we utilized receptor antagonists directed against the CB1. Receptor antagonist was administered prior to the agonist, as described in the experimental section to confirm that each antagonist blocked the respective receptor involved. As positive control, Δ-9-tetrahydrocannabinol (THC) was used. The result showed that THC increases the latency period (p < 0.05) which showed antinociceptive effects. The latency time was increased significantly, up to 60 min compared to vehicle treated groups. After 60 min, the effect decreased and was not significant when compared to the vehicle group. The MG alone group also showed a significant increase in the latency period compared to vehicle group and the significant antinociceptive effect was seen throughout the period of 120 min. The antinociceptive effect of THC was blocked by AM251. This was proved when the result showed that the latency time was significantly decreased at 30 min when compared to THC alone group (p < 0.05). However, when MG was given following prior administration of AM251, the latency time was prolonged and it was not statistically significant when compared to group with MG alone (Figure 6). These results suggested that MG did not exert the antinociceptive action through the CB1 receptor.

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