An accidental poisoning with mitragynine

Karinen, Ritva; Fosen, Jan Toralf; Rogde, Sidsel; Vindenes, Vigdis

doi:10.1016/j.forsciint.2014.10.025

Cited by 69 publications

(59 citation statements)

References 20 publications

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“…Postmortem screening of MG-related cases has shown that the drug concentrations in peripheral bloods were 0.23-1.06 mg/L (corresponding to 0.6-2.7 µM), 15,16) which are much less than the 50% lethal concentration values mentioned above (43.1 µM for HAE cells). Considering that diverse effects such as seizure were observed even at the lower MG concentrations, 17) it is assumed that at sublethal concentrations MG is capable of transmigrating itself across endothelial cell monolayer to extravascular tissues such as brain and muscle.…”

Section: Enhancement Of Endothelial Barrier Permeability By Mg Treatmentmentioning

confidence: 82%

Enhancement of Endothelial Barrier Permeability by Mitragynine

Matsunaga

Morikawa²,

Kamase

et al. 2017

Biological & Pharmaceutical Bulletin

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Persistent inhalation of mitragynine (MG), a major alkaloid in the leaves of Mitragyna speciosa, causes various systemic adverse effects such as seizure, diarrhea and arthralgias, but its toxicity to endothelial cells and effects on barrier function of the cells are poorly understood. In this study, we compared toxicities of MG and mitraphylline, another constituent of the leaves, against human aortic endothelial (HAE), bronchial BEAS-2B, neuronal SK-N-SH, hepatic HepG2, kidney HEK293, gastric MKN45, colon DLD1, lung A549, breast MCF7 and prostate LNCaP cells, and found that MG, but not mitraphylline, shows higher toxicity to HAE cells compared to the other cells. Forty-eight-hours incubation of HAE cells with a high concentration of MG (60 µM) provoked apoptotic cell death, which was probably due to signaling through enhanced reactive oxygen species (ROS) generation and resultant caspase activation. Treatment of the cells with MG at sublethal concentrations less than 20 µM significantly lowered transendothelial electrical resistance and elevated paracellular permeability, without affecting the cell viability. In addition, the MG-elicited lowering of the resistance was abolished by a ROS inhibitor N-acetyl-L-cysteine and augmented by H 2 O 2 and 9,10-phenanthrenequinone, which generates ROS through its redox cycle. These results suggest the contribution of ROS generation to the increase in endothelial barrier permeability.

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Section: Enhancement Of Endothelial Barrier Permeability By Mg Treatmentmentioning

confidence: 82%

Enhancement of Endothelial Barrier Permeability by Mitragynine

Matsunaga

Morikawa²,

Kamase

et al. 2017

Biological & Pharmaceutical Bulletin

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“…In 2014, Karinen et al (40) described a case report of an accidental poisoning with Mitragynine. The case was a middle-aged man with a dual diagnosis of substance abuse and mental illness found dead in bed (40).…”

Section: Resultsmentioning

confidence: 99%

Biochemical Benefits, Diagnosis, and Clinical Risks Evaluation of Kratom

Fluyau

Revadigar

2017

Front. Psychiatry

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BackgroundKratom (Mitragyna speciosa) is a tropical tree with a long history of traditional use in parts of Africa and Southeast Asia. Kratom is also known as Thom, Thang, and Biak. Its leaves and the teas brewed from them have long been used by people in that region to manage pain and opioid withdrawal and to stave off fatigue. Kratom is actually consumed throughout the world for its stimulant effects and as an opioid substitute (in form of tea, chewed, smoked, or ingested in capsules). Some case reports have associated kratom exposure with psychosis, seizures, intrahepatic cholestasis, other medical conditions, and deaths. The clinical manifestations of kratom effects are not well defined and the clinical studies are limited. Data research suggest that both stimulant and sedative dose-dependent effects do exist, in addition to antinociceptive, antidepressant activity, anxiolytic-like effects, and anorectic effects, but a growing concern for the drug’s effects and safety of use has resulted in national and international attention primarily due to an increase in hospital visits and deaths in several countries that are believed to have been caused by extracts of the plant. There is a dearth of double blind controlled studies. In this study, we aim to use existing literature to clarify both benefits and risks of kratom as well as its diagnosis evaluation as kratom misuse is an emerging trend in the Western world.MethodsLiterature review using databases such as Embase, Medline, PubMed, Cochrane Library, and Mendeley from 2007 to 2017 were evaluated by all authors to analyze current state on benefits, risks, and diagnosis evaluation of kratom (M. speciosa).ResultsData analysis suggested that kratom possesses some benefits such as stimulant and sedative effects as wells as antinociceptive effects. It seems to inhibit pro-inflammatory mediator release and vascular permeability and can enhance immunity. In addition, it may be an antidepressant and anorectic. However, kratom can cause intrahepatic cholestasis, seizure, arrhythmia, impair memory function, coma, and death. Psychological manifestations described are euphoria and feeling relaxed to severe symptoms such as aggression, hostility, and psychosis. Medical manifestations described are polyuria, dry mouth, vomiting, and jerky movements. Currently, liquid chromatography/mass spectrometry and ion mobility spectrometry (IMS) are suggested as the most promising to rapidly screen kratom products providing a positive success rate.ConclusionOur data analysis has not determined if biochemical benefits of kratom may prove to outweigh its toxicity and risks. On the contrary, it seems that its potential side effects outweigh the benefits, and severe and real health hazards can, insidiously, lead to death. Kratom clinical, psychological, and medical manifestations can be disturbing. Kratom (M. speciosa) use, among multiple compounds of the leaf, appear to be increasing in the Western world. Promising methods to accurately identify kratom compounds are still ongoing.

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“…Reported concentrations of verapamil were between 0.07 and 0.23 mM after a single oral dose of 80 mg [46]. Unfortunately, only for mitragynine (2.7 mM) [47] and glaucine (0.7 mM) [48], plasma concentrations were reported so far. For JWH 200 and WIN 55,212-2, concentration of related compounds might be considered and were reported to be below 0.4 mM [49].…”

Section: Caco-2 Transport Of Structurally Diverse Doamentioning

confidence: 99%