Kratom

Efectos

Mecanismo de acción

... Mitragynine (MIT), a mu-opioid agonist with antinociceptive and antitussive properties... Mitragynine, the principal alkaloid identified from Kratom, has been reported as a partial opioid agonist that produces morphine-like effects. An interesting minor alkaloid from Kratom, 7-hydroxymitragynine, has been reported to be more potent than morphine. Both Kratom alkaloids are reported as activators of supraspinal mu- and delta-opioid receptors, explaining their use by chronic narcotic users to alleviate opioid withdrawal symptoms.

Toxicidad

Mitragynine (MG), a principal alkaloidal constituent extracted from the Mitragyna speciosa Korth plant, is known to exert opioid-like activity. ... A previous study showed the involvement of opioid systems in the antinociceptive activity of MG in tail-pinch and hot-plate tests in mice. In this study, to clarify the opioid receptor subtypes involved in the antinociceptive action of MG, ... the effects of selective antagonists for mu-, delta- and kappa-opioid receptors on antinociception caused by intracerebroventricular (i.c.v.) injection of MG in tail-pinch and hot-plate tests in mice were investigated. Coadministration of a selective mu-opioid antagonist, cyprodime (1-10 μg, i.c.v.) and pretreatment with a selective mu1-opioid antagonist naloxonazine (1-3 μg, i.c.v.) significantly antagonized the antinociceptive activities of MG (10 μg, i.c.v.) and morphine (MOR, 3 μg, i.c.v.) in tail-pinch and hot-plate tests. Naltrindole (1-5 ng, i.c.v.), a selective delta-opioid antagonist, also blocked the effects of MG (10 μg, i.c.v.) without affecting MOR (3 μg, i.c.v.) antinociception. Nor-binaltorphimine, a selective kappa-opioid antagonist, significantly attenuated MG (10 μg, i.c.v.) antinociception in the tail-pinch test but not in the hot-plate test at the dose (1 μg, i.c.v.) that antagonized the antinociceptive effects of selective kappa-opioid agonist U50,488H in both tests, while it had no effect on MOR antinociception in either test. These results suggest that antinociception caused by i.c.v. MG is dominantly mediated by mu- and delta-opioid receptor subtypes, and that the selectivity of MG for supraspinal opioid receptor subtypes differs from that of MOR in mice. ... A case of kratom dependence is described in a 44-year-old man with a history of alcohol dependence and anxiety disorder. He demonstrated kratom dependence with withdrawal symptoms consisting of anxiety, restlessness, tremor, sweating, and substance craving

Farmacología

... LC-MS/MS analysis... was applied to quantify mitragynine in plasma samples from rats (n=8 per sampling time) treated with a single oral dose of 20 mg/kg. The following pharmacokinetic parameters were obtained (mean): maximum plasma concentration: 424 ng/mL; time to reach maximum plasma concentration: 1.26 hr; elimination half-life: 3.85 hr, apparent total clearance: 6.35 L/hr/kg, and apparent volume of distribution: 37.90 L/kg. Mitragyna speciosa (Kratom) is ... a drug of abuse. When monitoring its abuse in urine, several alkaloids and their metabolites should be considered. In previous studies, mitragynine (MG), its diastereomer speciogynine (SG), and paynantheine and their metabolites could be identified in rat and human urine using Liquid Chromatography - Tandem Mass Spectrometry (LC-MS(n)). In Kratom users' urine, in addition to MG and SG, more isomeric compounds were detected. To elucidate whether the diastereomer MG and SG speciociliatine (SC) and their metabolites represent additional compounds, phase I and II metabolites of SC were first identified in rat urine after administration of the pure alkaloid. Then, the identified rat metabolites were searched for in Kratom users' urine using the aforementioned LC-MS(n) procedure. Considering mass spectra and retention times, it could be confirmed that SC and its metabolites are so far the unidentified isomers in human urine. In conclusion, SC and its metabolites can be used as additional markers for Kratom use, especially from consumption of raw material or products containing a high amount of fruits from the Malaysian M. speciosa plant. ... The objective of this study is to identify phase I and II metabolites of mitragynine (MG) in rat and human urine after solid phase extraction (SPE) using liquid chromatography-linear ion trap mass spectrometry providing detailed structural information in MSn mode particularly with high resolution. The seven identified phase I metabolites indicated that MG was metabolized