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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 μ-opioid antagonist naloxone, δ-opioid antagonist naltrindole, μ1-opioid antagonist naloxonazine and κ-opioid antagonist norBNI on mitragynine-induced antinociception (35 mg/kg). 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. ap < 0.05 compared to mitragynine (35 mg/kg) alone group.
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f7-ijms-13-11427: Effects of μ-opioid antagonist naloxone, δ-opioid antagonist naltrindole, μ1-opioid antagonist naloxonazine and κ-opioid antagonist norBNI on mitragynine-induced antinociception (35 mg/kg). 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. ap < 0.05 compared to mitragynine (35 mg/kg) alone group.

Mentions: Naloxone (Nal), a non-selective opioid receptor antagonist, completely reversed the antinociceptive effects of MG when it showed a significant decrease in the latency time compared to MG alone. The same result was observed by naltrindole (NTI), a δ-receptor antagonist. Naloxonazine (NZI), a μ1-receptor antagonist did reduce the anticociceptive effect of MG, but it is not statistically significant. This indicates that MG may not only act specifically on μ1-receptor. However, norbinaltorpimine (norBNI) partially blocked the effect of MG and significantly decreased the latency time when compared with MG alone group from 30 min to 60 min, but not up to 120 min time. These findings indicate that MG may partially act via κ-receptor (Figure 7).


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 μ-opioid antagonist naloxone, δ-opioid antagonist naltrindole, μ1-opioid antagonist naloxonazine and κ-opioid antagonist norBNI on mitragynine-induced antinociception (35 mg/kg). 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. ap < 0.05 compared to mitragynine (35 mg/kg) alone group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7-ijms-13-11427: Effects of μ-opioid antagonist naloxone, δ-opioid antagonist naltrindole, μ1-opioid antagonist naloxonazine and κ-opioid antagonist norBNI on mitragynine-induced antinociception (35 mg/kg). 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. ap < 0.05 compared to mitragynine (35 mg/kg) alone group.
Mentions: Naloxone (Nal), a non-selective opioid receptor antagonist, completely reversed the antinociceptive effects of MG when it showed a significant decrease in the latency time compared to MG alone. The same result was observed by naltrindole (NTI), a δ-receptor antagonist. Naloxonazine (NZI), a μ1-receptor antagonist did reduce the anticociceptive effect of MG, but it is not statistically significant. This indicates that MG may not only act specifically on μ1-receptor. However, norbinaltorpimine (norBNI) partially blocked the effect of MG and significantly decreased the latency time when compared with MG alone group from 30 min to 60 min, but not up to 120 min time. These findings indicate that MG may partially act via κ-receptor (Figure 7).

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