Periodical
Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for μ-Opioid Receptor and Opioid-Like Behavioral Effects in Rats▪
| العنوان: | Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for μ-Opioid Receptor and Opioid-Like Behavioral Effects in Rats▪ |
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| المؤلفون: | Obeng, Samuel, Wilkerson, Jenny L., León, Francisco, Reeves, Morgan E., Restrepo, Luis F., Gamez-Jimenez, Lea R., Patel, Avi, Pennington, Anna E., Taylor, Victoria A., Ho, Nicholas P., Braun, Tobias, Fortner, John D., Crowley, Morgan L., Williamson, Morgan R., Pallares, Victoria L.C., Mottinelli, Marco, Lopera-Londoño, Carolina, McCurdy, Christopher R., McMahon, Lance R., Hiranita, Takato |
| المصدر: | The Journal of Pharmacology and Experimental Therapeutics; March 2021, Vol. 376 Issue: 3 p410-427, 18p |
| مستخلص: | Relationships between µ-opioid receptor (MOR) efficacy and effects of mitragynine and 7-hydroxymitragynine are not fully established. We assessed in vitro binding affinity and efficacy and discriminative stimulus effects together with antinociception in rats. The binding affinities of mitragynine and 7-hydroxymitragynine at MOR (Kivalues 7709 and 77.9 nM, respectively) were higher than their binding affinities at κ- (KOR) or δ-opioid receptors (DOR). [35S]GTPγS stimulation at MOR demonstrated that mitragynine was an antagonist, whereas 7-hydroxymitragynine was a partial agonist (Emax= 41.3%). In separate groups of rats discriminating either morphine (3.2 mg/kg) or mitragynine (32 mg/kg), mitragynine produced a maximum of 72.3% morphine-lever responding, and morphine produced a maximum of 65.4% mitragynine-lever responding. Other MOR agonists produced high percentages of drug-lever responding in the morphine and mitragynine discrimination assays: 7-hydroxymitragynine (99.7% and 98.1%, respectively), fentanyl (99.7% and 80.1%, respectively), buprenorphine (99.8% and 79.4%, respectively), and nalbuphine (99.4% and 98.3%, respectively). In the morphine and mitragynine discrimination assays, the KOR agonist U69,593 produced maximums of 72.3% and 22.3%, respectively, and the DOR agonist SNC 80 produced maximums of 34.3% and 23.0%, respectively. 7-Hydroxymitragynine produced antinociception; mitragynine did not. Naltrexone antagonized all of the effects of morphine and 7-hydroxymitragynine; naltrexone antagonized the discriminative stimulus effects of mitragynine but not its rate-decreasing effects. Mitragynine increased the potency of the morphine discrimination yet decreased morphine antinociception. Here we illustrate striking differences in MOR efficacy, with mitragynine having less than 7-hydroxymitragynine. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 00223565 15210103 |
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| DOI: | 10.1124/jpet.120.000189 |