Physicochemical Characterization of Mitragyna speciosa Alkaloid Extract and Mitragynine using In Vitro High Throughput Assays

Kong, Wai Mun; Chik, Zamri; Mohamed, Zahurin; Alshawsh, Mohammed Abdullah

doi:10.2174/1386207320666171026121820

Cited by 18 publications

(13 citation statements)

References 38 publications

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“…given that K i and K I of mitragynine towards CYP2D6 and CYP3A were within concentrations reported for autopsy blood samples from kratom-related deaths (1-13 vs. 0.04-12 μM). Although mitragynine has been reported to bind extensively to plasma proteins (f u,p , 0.02-0.15) (Kong et al, 2017;Obeng et al, 2019), the partitioning of mitragynine from blood into the liver, as well as whether uptake transporters influence intracellular mitragynine concentrations, is not known.…”

Section: Discussionmentioning

confidence: 99%

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

Tanna

Tian

Cech

et al. 2020

J Pharmacol Exp Ther

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Abbreviations: AUC, area under the plasma concentration-time curve; AUCR, ratio of AUC in presence to absence of inhibitor; CYP, cytochrome P450; DEA, Drug Enforcement Administration; f u,p , fraction unbound in human plasma; HIMs, human intestinal microsomes; HLMs, human liver microsomes; IVIVE, in vitro to in vivo extrapolation; k inact , maximum rate of inactivation; K I , time-dependent inhibition constant; K i , reversible inhibition constant; TDI, timedependent inhibition; UPLC-MS/MS, ultra-high performance liquid chromatography-tandem mass spectrometry This article has not been copyedited and formatted. The final version may differ from this version.

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Section: Discussionmentioning

confidence: 99%

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

Tanna

Tian

Cech

et al. 2020

J Pharmacol Exp Ther

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“…However, organic solvents such as acetone, acetic acid, alcohols, chloroform, and diethyl ether can solubilize mitragynine and also provide fluorescent solutions . The solubility limit of mitragynine in aqueous solution at pH 4 and pH 7 is 130 and 83 μM, respectively . Although mitragynine has reasonable stability in neutral and basic media (∼3.5% is degraded after 3 h at pH 7), it showed chemical instability in acidic media over time (∼26% degraded after 1–2 h at pH 1.2). ,, The first chemical structure of mitragynine was determined in 1965, and a more recent crystal structure obtained from ethanol solvent has also been reported. , After its structural elucidation, three total syntheses, along with one formal syntheses of (−)-mitragynine were reported. ,− Moreover, various semisynthetic approaches toward more potent mitragynine derivatives such as 7-hydroxymitragynine and mitragynine pseudoindoxyl were also reported.…”

Section: Chemical Properties and Synthesismentioning

confidence: 99%

“…After absorption, subsequent first-pass metabolism (phase I and II) in the liver is responsible for the majority of mitragynine metabolism (Figure ). Moderately high plasma protein binding in human plasma (85.35 ± 1.22%, bound at 10 μM) also contributes to mitragynine’s turnover . Among CYP isoforms, CYP3A4 plays a major role along with CYP2D6 and CYP2C9.…”

Section: Drug Metabolism and Pharmacokineticsmentioning

confidence: 99%

DARK Classics in Chemical Neuroscience: Kratom

Han

Schmitt

Gilliland

2019

ACS Chem. Neurosci.

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The psychoactive plant kratom is a native plant to Southeast Asia, and its major bioactive alkaloid is mitragynine. Mitragynine exerts its analgesic properties by acting on the opioid receptors. One of its active metabolites, 7-hydroxymytraginine, is found to be 40 times more potent than mitragynine and 10 times more potent than morphine. Interestingly, current research suggests that mitragynine behaves as an atypical opioid agonist, possessing analgesic activity with less severe side effects than those of typical opioids. Although Thailand and Malaysia have criminalized the use, possession, growing, or selling of kratom due to its abuse potential, kratom still remains unregulated in the United States. The U.S. Drug Enforcement Agency (DEA) listed kratom as a "drug of concern" in 2008 with the intent to temporarily place mitragynine and 7hydroxymitragynine onto Schedule I of the Controlled Substances Act. However, responses from the general public, U.S. Congress, and Kratom Alliances had the DEA retract their intent. Kratom is currently marketed in the United States as a dietary or herbal supplement used to treat chronic pain, anxiety, and depression with over $207 million in annual sales in the United States alone. Here, we will review the traditional and medicinal uses of kratom along with the synthesis of its bioactive ingredients and their pharmacology, metabolism, and structure−activity relationships. The importance in society of this currently controversial substance will also be discussed.

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“…In fact, the physicochemical properties of any novel potential drug candidate should be characterized. These properties include solubility, lipophilicity, and chemical stability in acidic and alkaline environments or buffers used in biological assays [25].…”

Section: Introductionmentioning

confidence: 99%

“…These properties include solubility, lipophilicity, and chemical stability in acidic and alkaline environments or buffers used in biological assays [25].…”

Section: Introductionmentioning

confidence: 99%

Pharmaceutical and Safety Profile Evaluation of Novel Selenocompounds with Noteworthy Anticancer Activity

et al. 2022

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Prior studies have reported the potent and selective cytotoxic, pro-apoptotic, and chemopreventive activities of a cyclic selenoanhydride and of a series of selenoesters. Some of these selenium derivatives demonstrated multidrug resistance (MDR)-reversing activity in different resistant cancer cell lines. Thus, the aim of this study was to evaluate the pharmaceutical and safety profiles of these selected selenocompounds using alternative methods in silico and in vitro. One of the main tasks of this work was to determine both the physicochemical properties and metabolic stability of these selenoesters. The obtained results proved that these tested selenocompounds could become potential candidates for novel and safe anticancer drugs with good ADMET parameters. The most favorable selenocompounds turned out to be the phthalic selenoanhydride (EDA-A6), two ketone-containing selenoesters with a 4-chlorophenyl moiety (EDA-71 and EDA-73), and a symmetrical selenodiester with a pyridine ring and two selenium atoms (EDA-119).

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Physicochemical Characterization of Mitragyna speciosa Alkaloid Extract and Mitragynine using In Vitro High Throughput Assays

Abstract: The obtained ADME and cytotoxicity data demonstrated that both MSAE and mitragynine have poor bioavailability and have the potential to be significantly cytotoxic.

Cited by 18 publications

References 38 publications

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

DARK Classics in Chemical Neuroscience: Kratom

Pharmaceutical and Safety Profile Evaluation of Novel Selenocompounds with Noteworthy Anticancer Activity

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