Glucuronidation of Psilocin and 4-Hydroxyindole by the Human UDP-Glucuronosyltransferases

Manevski, Nenad; Kurkela, Mika; Höglund, Camilla; Mauriala, Timo; Court, Michael H.; Yli‐Kauhaluoma, Jari; Finel, Moshe

doi:10.1124/dmd.109.031138

Cited by 50 publications

(41 citation statements)

References 33 publications

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“…After absorption within circulatory system the conversion of psilocin to glucuronide is mediated by UGT1A9. 126 Other identified psilocin metabolites, namely 4-hydroxy-3-yl-acetic acid 4HIAA, 4-hydroxy-3-yl-acetaldehyde 4HIA, and 4-hydroxytryptophol 4I-IT, are the products of its deamination and oxidation. 114,122 …”

Section: Methods Of Qualitative Analysis and Isolationmentioning

confidence: 99%

Fungal Hallucinogens Psilocin, Ibotenic Acid, and Muscimol

Stebelska

2013

Therapeutic Drug Monitoring

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Psychoactive drugs of fungal origin, psilocin, ibotenic acid, and muscimol among them have been proposed for recreational use and popularized since the 1960s, XX century. Despite their well-documented neurotoxicity, they reached reputation of being safe and nonaddictive. Scientific efforts to find any medical application for these hallucinogens in psychiatry, psychotherapy, and even for religious rituals support are highly controversial. Even if they show any healing potential, their usage in psychotherapy is in some cases inadequate and may additionally harm seriously suffering patients. Hallucinogens are thought to reduce cognitive functions. However, in case of indolealkylamines, such as psilocin, some recent findings suggest their ability to improve perception and mental skills, what would motivate the consumption of "magic mushrooms." The present article offers an opportunity to find out what are the main symptoms of intoxication with mushrooms containing psilocybin/psilocin, muscimol, and ibotenic acid. The progress in analytical methods for detection of them in fungal material, food, and body fluids is reviewed. Findings on the mechanisms of their biologic activity are summarized. Additionally, therapeutic potential of these fungal psychoactive compounds and health risk associated with their abuse are discussed.

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Section: Methods Of Qualitative Analysis and Isolationmentioning

confidence: 99%

Fungal Hallucinogens Psilocin, Ibotenic Acid, and Muscimol

Stebelska

2013

Therapeutic Drug Monitoring

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“…Total RNA was isolated with RNA-Bee system (Tel-Test Inc., Friendswood, TX), according to the manufacturer's manual and as described previously . Levels of UGT1A1, UGT1A9, and UGT2B7 mRNAs were determined by real-time polymerase chain reaction (PCR) (model 7300; Applied Biosystems, Foster City, CA) with SYBR Green detection as previously described with minor modifications (Manevski et al, 2010). Quantitative PCRs (25 l) included SYBR Green 2ϫ Master Mix (Applied Biosystems), 10 l of diluted cDNA, and 100 nM of each primer (200 nM for 18S RNA).…”

Section: Methodsmentioning

confidence: 99%

Diabetes Mellitus Reduces Activity of Human UDP-Glucuronosyltransferase 2B7 in Liver and Kidney Leading to Decreased Formation of Mycophenolic Acid Acyl-Glucuronide Metabolite

Dostálek¹,

Court²,

Hazarika³

et al. 2010

Drug Metab Dispos

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ABSTRACT:Mycophenolic acid (MPA) is an immunosuppressive agent commonly used after organ transplantation. Altered concentrations of MPA metabolites have been reported in diabetic kidney transplant recipients, although the reason for this difference is unknown. We aimed to compare MPA biotransformation and UDP-glucuronosyltransferase (UGT) expression and activity between liver (n ‫؍‬ 16) and kidney (n ‫؍‬ 8) from diabetic and nondiabetic donors. Glucuronidation of MPA, as well as the expression and probe substrate activity of UGTs primarily responsible for MPA phenol glucuronide (MPAG) formation (UGT1A1 and UGT1A9), and MPA acyl glucuronide (AcMPAG) formation (UGT2B7), was characterized. We have found that both diabetic and nondiabetic human liver microsomes and kidney microsomes formed MPAG with similar efficiency; however, AcMPAG formation was significantly lower in diabetic samples. This finding is supported by markedly lower glucuronidation of the UGT2B7 probe zidovudine, UGT2B7 protein, and UGT2B7 mRNA in diabetic tissues. UGT genetic polymorphism did not explain this difference because UGT2B7*2 or *1c genotype were not associated with altered microsomal UGT2B7 protein levels or AcMPAG formation. Furthermore, mRNA expression and probe activities for UGT1A1 or UGT1A9, both forming MPAG but not AcMPAG, were comparable between diabetic and nondiabetic tissues, suggesting the effect may be specific to UGT2B7-mediated AcMPAG formation. These findings suggest that diabetes mellitus is associated with significantly reduced UGT2B7 mRNA expression, protein level, and enzymatic activity of human liver and kidney, explaining in part the relatively low circulating concentrations of AcMPAG in diabetic patients.

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“…Indeed, more than 80% of the psilocin administered to humans is metabolized to psilocin glucuronides. In vitro psilocin glucuronidation also has been studied using 19 recombinant human UDP glucuronosyltransferases of the subfamilies 1A, 2A and 2B [10]. Holzmann et al [1] have shown that psilocin may undergo enzymatic oxidation in humans to form 4-hydroxytryptophole (4-HT) and 4-hydroxyindole-3-acetaldehyde, which may be further metabolized to 4-HIAA.…”

Section: Introductionmentioning

confidence: 99%

14C-Psilocin tissue distribution in pregnant rats after intravenous administration

Law

Poon

Chui

et al. 2014

FFHD

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Background: Many species of hallucinogenic mushrooms have been found in the genusPsilocybe. The main psychoactive chemicals of Psilocybe mushrooms are psilocin and its phosphoryloxy derivative, psilocybin. In addition to its psychedelic effects, psilocybin is an effective agent to lift the mood of depressed patients with terminal cancers. Objective:To study the dispositional kinetics of 14 C-psilocin in pregnant rats after intravenous injection, to calculate tissue dose surrogates i.e., tissue 14 C concentration and area under the concentration-time curve using the experimental data, to quantify trans-placental passage of psilocin and/or its metabolites, and to identify new psilocin metabolite(s) in rat urine.Methods: A group of 15 pregnant Wistar rats weighing between 0.30-0.36 kg was used in the study. Each rat was given a single dose of 7.5 mg/kg 14 C-psilocin i.v. Three rats were randomly selected and sacrificed at 0.5, 1.0, 2.0, 4.0, and 8.0 hr post-dosing. The maternal and fetal tissues were quickly removed and the radioactivity in these tissues determined by liquid scintillation counting. In a separate study, urine samples were collected from 6 male Wistar rats after administering 15 mg/kg of unlabeled psilocin i.p. The urine samples were collected and extracted by chloroform-methanol (9:1 v/v) and analyzed using a gas chromatograph/mass spectrometer. Results:14 C-Psilocin crossed the placental barrier of pregnant rats readily after i.v.administration; maternal tissue 14 C concentrations were found to be much higher than those in fetal tissues. The areas under the curve for maternal tissues also were much higher than the fetal tissues. In general, maternal tissues could be divided into the fast eliminating organ group, which

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Glucuronidation of Psilocin and 4-Hydroxyindole by the Human UDP-Glucuronosyltransferases

Cited by 50 publications

References 33 publications

Fungal Hallucinogens Psilocin, Ibotenic Acid, and Muscimol

Fungal Hallucinogens Psilocin, Ibotenic Acid, and Muscimol

Diabetes Mellitus Reduces Activity of Human UDP-Glucuronosyltransferase 2B7 in Liver and Kidney Leading to Decreased Formation of Mycophenolic Acid Acyl-Glucuronide Metabolite

14C-Psilocin tissue distribution in pregnant rats after intravenous administration

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