Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa

Life Sciences ◽  
2004 ◽  
Vol 74 (17) ◽  
pp. 2143-2155 ◽  
Author(s):  
Kenjiro Matsumoto ◽  
Syunji Horie ◽  
Hayato Ishikawa ◽  
Hiromitsu Takayama ◽  
Norio Aimi ◽  
...  
Keyword(s):  
Opioid Analgesic ◽  
Antinociceptive Effect ◽  
Medicinal Herb ◽  
Mitragyna Speciosa ◽  
Orally Active

Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa

Life Sciences ◽  
2005 ◽  
Vol 78 (1) ◽  
pp. 2-7 ◽  
Author(s):  
Kenjiro Matsumoto ◽  
Syunji Horie ◽  
Hiromitsu Takayama ◽  
Hayato Ishikawa ◽  
Norio Aimi ◽  
...  
Keyword(s):  
Medicinal Herb ◽  
Withdrawal Symptoms ◽  
Mitragyna Speciosa

Indole Alkaloids of a Thai Medicinal Herb,Mitragyna speciosa,that has Opioid Agonistic Effect in Guinea-Pig Ileum

Planta Medica ◽  
2005 ◽  
Vol 71 (3) ◽  
pp. 231-236 ◽  
Author(s):  
Syunji Horie ◽  
Fumi Koyama ◽  
Hiromitsu Takayama ◽  
Hayato Ishikawa ◽  
Norio Aimi ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Indole Alkaloids ◽  
Medicinal Herb ◽  
Guinea Pig Ileum ◽  
Mitragyna Speciosa ◽  
Agonistic Effect

Exogenous gaseous superoxide potentiates the antinociceptive effect of opioid analgesic agents

1996 ◽  
Vol 45 (9) ◽  
pp. 473-478 ◽  
Author(s):  
N. Goldstein ◽  
T. Lewin ◽  
A. Kamensky ◽  
V. Dubinin ◽  
S. Baumann ◽  
...  
Keyword(s):  
Opioid Analgesic ◽  
Antinociceptive Effect ◽  
Analgesic Agents

scholarly journals Accelerated Solvent Extractions (ASE) of Mitragyna speciosa Korth. (Kratom) Leaves: Evaluation of Its Cytotoxicity and Antinociceptive Activity

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3704
Author(s):  
Yong Sean Goh ◽  
Thiruventhan Karunakaran ◽  
Vikneswaran Murugaiyah ◽  
Rameshkumar Santhanam ◽  
Mohamad Hafizi Abu Bakar ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Antinociceptive Effect ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Total Phenolic ◽  
Leaf Extracts ◽  
Hek 293 ◽  
Mitragyna Speciosa ◽  
Botanical Extract ◽  
Ethanolic Leaf Extract

Mitragyna speciosa Korth (kratom) is known for its psychoactive and analgesic properties. Mitragynine is the primary constituent present in kratom leaves. This study highlights the utilisation of the green accelerated solvent extraction technique to produce a better, non-toxic and antinociceptive active botanical extract of kratom. ASE M. speciosa extract had a dry yield (0.53–2.91 g) and showed a constant mitragynine content (6.53–7.19%) when extracted with organic solvents of different polarities. It only requires a shorter extraction time (5 min) and a reduced amount of solvents (less than 100 mL). A substantial amount of total phenolic (407.83 ± 2.50 GAE mg/g and flavonoids (194.00 ± 5.00 QE mg/g) were found in ASE kratom ethanol extract. The MTT test indicated that the ASE kratom ethanolic leaf extract is non-cytotoxic towards HEK-293 and HeLa Chang liver cells. In mice, ASE kratom ethanolic extract (200 mg/kg) demonstrated a better antinociceptive effect compared to methanol and ethyl acetate leaf extracts. The presence of bioactive indole alkaloids and flavonols such as mitragynine, paynantheine, quercetin, and rutin in ASE kratom ethanolic leaf extract was detected using UHPLC-ESI-QTOF-MS/MS analysis supports its antinociceptive properties. ASE ethanolic leaf extract offers a better, safe, and cost-effective choice of test botanical extract for further preclinical studies.

scholarly journals Antinociceptive Activity of Aqueous Fraction of Kratom Leaves Mitragyna speciosa Korth.) on Male Swiss Albino Mice

2018 ◽  
Vol 23 (2) ◽  
pp. 91
Author(s):  
Widia Indri Nugraha ◽  
Robiyanto Robiyanto ◽  
Sri Luliana
Keyword(s):  
Antinociceptive Effect ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Latency Time ◽  
Aqueous Fraction ◽  
Swiss Albino Mice ◽  
Mitragyna Speciosa ◽  
Albino Mice

Kratom (Mitragyna speciosa Korth.) has been known to have an analgesic opioid effect (antinociceptive). The major compound of kratom leaf is mitraginin, which has strong affinity on opioid receptor. The aim of this research is to prove antinociceptive effect of aqueous fraction of kratom leaf and its effective dose. The simplicia of kratom leaf was extracted with methanol 96%. Methanol extract fractioned with n-hexane, dichloromethane, ethyl acetate, and aquadest. This research used hot plate method on male Swiss Albino mice. The subject divided to 5 groups, negative control group, morphine 5,46 mg/kgBW, aqueous fraction 140, 240 and 560 mg/kgBW. Latency time was measured every 15 minutes over 2 hours period. Analytic statistical of latency time using One Way ANOVA shows that the aqueous fraction at the dose of 140, 280 and 560 mg/kgBW significantly differentiate with negative control group and positive control group. The antinociceptive effect increases with increasing doses. The three doses showed that the antinociceptive effect was no better than the positive control (Morphine)

scholarly journals Comparative evaluation of phasic and chemical antinociceptive action of a conventional and a novel anticonvulsants in experimental models of tail flick and formalin test

2019 ◽  
Vol 7 (2) ◽  
pp. 323
Author(s):  
Saurabh Kansal ◽  
Rohan Sirohi ◽  
Ruchika Agarwal
Keyword(s):  
Analgesic Effect ◽  
Formalin Test ◽  
Opioid Analgesic ◽  
Late Phase ◽  
Antinociceptive Effect ◽  
Experimental Models ◽  
Phase Response ◽  
Tail Flick ◽  
Second Phase ◽  
Tail Flick Test

Background: Some antiepileptic drugs have been shown to be clinically efficacious in treatment of neuropathic pain and are being used by clinician.Methods: This study determined the analgesic effect of gabapentin (a conventional anticonvulsant) and levitiracetam (a novel anticonvulsant) in rats in different types of acute and chronic nociceptive test like tail flick and formalin test and compared its potency with a conventional non opioid analgesic diclofenac.Results: Per oral administration of gabapentin produced no any marked effect on early phase response of formalin test but significantly suppressed the late phase response while levitiracetam produced no any type of significant effect in both phases. In tail flick test gabapentin as well as levitiracetam produced no any significant analgesic effect while diclofenac produced significant reduction of pain in tail flick test as well as in both phases of formalin test.Conclusions: Thus, we have observed that gabapentin produced antinociception in chronic pain as second phase of formalin test reflects chronic inflammatory pain while levitiracetam did not produce any type of antinociceptive effect as it could not suppress the pain significantly in both tail flick and formalin test. 

scholarly journals TO STUDY THE ANTINOCICEPTIVE EFFECT OF CINNARIZINE ALONE AND IN COMBINATION WITH TRAMADOL IN ALBINO RATS BY TAIL FLICK METHOD

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Rajiv Kumar ◽  
Aasim Shakeel ◽  
Manju Gari ◽  
Uma Shankar Prasad Keshri
Keyword(s):  
Reaction Time ◽  
Opioid Analgesic ◽  
Antinociceptive Effect ◽  
Radiant Heat ◽  
Antinociceptive Activity ◽  
Albino Rats ◽  
Tail Flick ◽  
Withdrawal Time ◽  
Tail Flick Test ◽  
Standard Drug

Background: Pain is the most common reason for physician consultation in most countries. It is a major symptom in many medical conditions, and can interfere with a person's quality of life and general functioning. Acute pain is usually managed with medications such as analgesics and anesthetics. Cinnarizine is a piperazine derivative and Tramadol is an opioid analgesic. Cinnarizine is also a calcium channel blocker. So, in the present study an attempt has been made to access the antinociceptive activity of Cinnarizine alone & in combination with standard drug Tramadol with the hope of pharmacological synergism and better relief from pain. Material & Methods: 4 rats in 6 groups were weighed & colour coded. Basal reaction time to radiant heat was taken. Tail withdrawal time was recorded as the end point. Reaction time was taken at 0, 30 & 60 minutes on day 0, 7, 14, 21 & 28. Result: All observation were done by the ANOVA followed by post hoc Tukey’s. It is seen that Cinnarizine alone (in both doses) has antinociceptive activity but that is not statistically significant. But when it is given along with Tramadol it potentiates antinociceptive activity of Tramadol which is statistically significant. Conclusion: The result of this study conclude that Cinnarizine alone has antinociceptive activity in both doses (i.e 2.5mg/kg & 5mg/kg) but it is statistically not significant. Tramadol shows higher antinociception with Cinnarizine in dose of 5mg/kg than with 2.5mg/kg. Keywords: Antinociception, Cinnarizine, Tramadol, Tail flick test, Albino rats

scholarly journals The synergistic antinociceptive effect of lornoxicam in combination with tramadol

2013 ◽  
Vol 3 (3) ◽  
pp. 238-242
Author(s):  
Amela Saračević ◽  
Fahir Bečić
Keyword(s):  
Analgesic Effect ◽  
Opioid Analgesic ◽  
Antinociceptive Effect ◽  
Subcutaneous Administration ◽  
Opioid Analgesics ◽  
Antinociceptive Effects ◽  
Significant Difference ◽  
Specific Receptors ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Introduction: One of the most important priorities in therapy is pain control. Therefore, many different groups of drugs are being used for this purpose, primarily opioid analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Opioid analgesic tramadol, by binding to specific receptors, modulates the perception and response to painful stimuli and inhibits transmitting and further processing of pain impulses. Lornoxicam, which belongs to the oxicam class of NSAIDs, is a non-selective cyclooxygenase inhibitor with strong analgesic and anti-inflammatory effects, and better tolerance profile. Preliminary research, which requires further verification, suggests that lornoxicam may be a better alternative or adjunctive therapy to opioid analgesics in the treatment of moderate to severe pain. The aim of this study was to investigate antinociceptive effects of lornoxicam, as well as the combination of lornoxicam with tramadol.Methods: Analgesic effect of combination of lornoxicam and tramadol or lornoxicam applied alone was examined on female albino mice, using a hot plate method. Measurements were made 30, 60, 90 and 120 minutes after intraperitoneal and subcutaneous administration, in dose of 10 mg/kg.Results: Combination of lornoxicam and tramadol, applied intraperitoneally, increases the threshold of sensitivity to painful stimuli, which was not the case with subcutaneous administration.Conclusions: Lornoxicam significantly increases analgesic effect when applied intraperitoneally in combination with tramadol. On the other hand, lornoxicam in combination with tramadol, did not increase the threshold of sensitivity to painful stimuli with significant difference, after subcutaneous administration

Synergistic combinations of the dual enkephalinase inhibitor PL265 given orally with various analgesic compounds acting on different targets, in a murine model of cancer-induced bone pain

2017 ◽  
Vol 14 (1) ◽  
pp. 25-38 ◽  
Author(s):  
Sara González-Rodríguez ◽  
Hervé Poras ◽  
Luis Menéndez ◽  
Ana Lastra ◽  
Tanja Ouimet ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Receptor Antagonist ◽  
Bone Pain ◽  
Chronic Treatment ◽  
Opioid Analgesic ◽  
Antinociceptive Effect ◽  
Cb1 Receptor ◽  
Endogenous Opioids ◽  
Cb2 Receptor ◽  
Analgesic Drugs

AbstractBackgroundThe first line pharmacological treatment of cancer pain is morphine and surrogates but a significant pain relief and a reduction of the side-effects of these compounds makes it necessary to combine them with other drugs acting on different targets. The aim of this study was to measure the antinociceptive effect on cancer-induced bone pain resulting from the association of the endogenous opioids enkephalin and non-opioid analgesic drugs. For this purpose, PL265 a new orally active single dual inhibitor of the two degrading enkephalins enzymes, neprilysin (NEP) and aminopeptidase N (APN) was used. It strictly increased the levels of enkephalin at their sites of releases. The selected non-opioid compounds are: gabapentin, A-317491 (P2X3receptor antagonist), ACEA (CB1 receptor antagonist), AM1241 (CB2 receptor antagonist), JWH-133 (CB2 receptor antagonist), URB937 (FAAH inhibitor), and NAV26 (Nav1.7 channel blocker).MethodsExperiments. Experiments were performed in 5–6 weeks old (26–33g weight) C57BL/6 mice. Cell culture and cell inoculation. B16-F10 melanoma cells were cultured and when preconfluent, treated and detached. Finally related cells were resuspended to obtain a concentration of 2×106cells/100μL. Then 105cells were injected into the right tibial medullar cavity. Control mice were treated by killed cells by freezing.Behavioural studies. Thermal withdrawal latencies were measured on a unilatered hot plate (UHP) maintained at 49±0.2 °C.Mechanical threshold values were obtained by performing the von Frey test using the “up and down” method. To evaluate the nature (additive or synergistic) of the interactions between PL265 and different drugs, an isobolographic analysis following the method described by Tallarida was performed.ResultsThe results demonstrate the ability of PL265, a DENKI that prevents the degradation of endogenous ENKs, to counteract cancer-induced bone thermal hyperalgesia in mice, by exclusively stimulating peripheral opioid receptors as demonstrated by used of an opioid antagonist unable to enter the brain. The development of such DENKIs, endowed with druggable pharmacokinetic characteristics, such as good absorption by oral route, can be considered as an important step in the development of much needed novel antihyperalgesic drugs. Furthermore, all the tested combinations resulted in synergistic antihyperalgesic effects. As shown here, the greatest synergistic antinociceptive effect (doses could be lowered by 70%) was produced by the combination of PL265 with the P2X3receptor antagonist (A-317491), cannabinoid CB1 receptor agonist (exogenous, ACEA and endogenous URB937-protected-AEA) and Nav1.7 blocker (NAV26) whose mechanism of action involves the direct activation of the enkephalinergic system.ConclusionsThese multi-target-based antinociceptive strategies using combinations of non-opioid drugs with dual inhibitors of enkephalin degrading enzymes may bring therapeutic advantages in terms of efficacy and safety by allowing the reduction of doses of one of the compounds or of both, which is of the utmost interest in the chronic treatment of cancer pain.ImplicationsThis article presents synergistic antinociceptive effect produced by the combination of PL265 with non-opioid analgesic drugs acting via unrelated mechanisms. These multi-target-based antinociceptive strategies may bring therapeutic advantages by allowing the reduction of doses, which is of great interest in the chronic treatment of cancer pain.

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