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Sample records for bufotenine

  1. Bufotenine: toward an understanding of possible psychoactive mechanisms.

    Science.gov (United States)

    McBride, M C

    2000-01-01

    A review of the neuropharmacology of the alleged hallucinogen bufotenine is presented, including recent experimental results showing activity similar to LSD and other known hallucinogens (psilocin and 5-MeO-DMT) at the purported hallucinogenic serotonin (5-HT) receptors, 5-HT2A and 5-HT2C. In addition, current reports of computer modeling of the receptors and ligand binding sites give evidence of bufotenine's ability to bind and activate these receptors. While binding and activation of the purported hallucinogenic receptors are not the full extent of the hallucinogenic signature, this evidence shows support for the rationale that the reported lack of the drug's classic hallucinogenic response in human experiments is due to poor ability to cross the blood brain barrier (BBB), not lack of activation of the appropriate brain receptors. Further evidence is reviewed that in some physiological states, some drugs with characteristics similar to bufotenine which do not normally cross the BBB, cross it and enter the brain. While direct human experimental evidence of bufotenine's hallucinogenic activity seems lacking, the above combined factors are considered, and possible explanations of bufotenine's reported psychoactivity are suggested. Additionally, updated experimental models testing the possible nature of bufotenine's hallucinogenic potential are proposed.

  2. Analysis of psilocin, bufotenine and LSD in hair.

    Science.gov (United States)

    Martin, Rafaela; Schürenkamp, Jennifer; Gasse, Angela; Pfeiffer, Heidi; Köhler, Helga

    2015-03-01

    A method for the simultaneous extraction of the hallucinogens psilocin, bufotenine, lysergic acid diethylamide (LSD) as well as iso-LSD, nor-LSD and O-H-LSD from hair with hydrochloride acid and methanol is presented. Clean-up of the hair extracts is performed with solid phase extraction using a mixed-mode cation exchanger. Extracts are measured with liquid chromatography coupled with electrospray tandem mass spectrometry. The method was successfully validated according to the guidelines of the 'Society of Toxicological and Forensic Chemistry' (GTFCh). To obtain reference material hair was soaked in a solution of the analytes in dimethyl sulfoxide/methanol to allow incorporation into the hair. These fortified hair samples were used for method development and can be employed as quality controls. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Development of a LC-MS/MS method to analyze 5-methoxy-N,N-dimethyltryptamine and bufotenine, and application to pharmacokinetic study.

    Science.gov (United States)

    Shen, Hong-Wu; Jiang, Xi-Ling; Yu, Ai-Ming

    2009-04-01

    INTRODUCTION: 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive indolealkylamine substance that has been used for recreational purpose and may lead to fatal toxicity. While 5-MeO-DMT is mainly inactivated via deamination, it is O-demethylated to an active metabolite, bufotenine. Quantitation of 5-MeO-DMT and bufotenine is essential to understand the exposure to and the effects of drug and metabolite. This study, therefore, aimed to develop and validate a LC-MS/MS method for simultaneous analysis of 5-MeO-DMT and bufotenine in mouse serum. METHODS: A simple protein precipitation method coupled with an optimal gradient elution was used for sample preparation and separation. Detection of 5-MeO-DMT and bufotenine was accomplished using multiple reaction monitoring of m/z 219.2→174.2 and 205.2→160.2, respectively, in the positive ion mode. 5-Methyl-N,N-dimethyltrypamine (m/z 203.2→158.3) was used as internal standard for quantification. Accuracy and precision were determined after the analyses of quality control samples. Validated assay was then employed to determine drug and metabolite concentrations in serum samples collected from mice at different time points after intraperitoneal administration of 5-MeO-DMT (2 mg/kg). RESULTS: With a total run time of 9 min, 5-MeO-DMT and bufotenine were eluted at 2.8 and 5.6 min, respectively. The assay was linear over the range 0.90-5,890 ng/mL (1.12-7,360 pg on-column) for 5-MeO-DMT and 2.52-5,510 ng/mL (3.14-6,890 pg) for bufotenine. Intra- and inter-day precision and accuracy were within 15% for both analytes. The recovery of each analyte from 20 µL of serum containing 8.08, 72.7 and 655 ng/mL of 5-MeO-DMT and 7.56, 68.1 and 613 ng/mL of bufotenine was more than 75%. Pharmacokinetic analysis revealed that the systemic exposure (area under the curve) to metabolite bufotenine was about 1/14 of that to 5-MeO-DMT. CONCLUSION: This LC-MS/MS method is a sensitive and reliable assay for quantitation of blood 5-Me

  4. Determination of psilocin, bufotenine, LSD and its metabolites in serum, plasma and urine by SPE-LC-MS/MS.

    Science.gov (United States)

    Martin, Rafaela; Schürenkamp, Jennifer; Gasse, Angela; Pfeiffer, Heidi; Köhler, Helga

    2013-05-01

    A validated method for the simultaneous determination of psilocin, bufotenine, lysergic acid diethylamide and its metabolites in serum, plasma and urine using liquid chromatography-electrospray ionization/tandem mass spectrometry was developed. During the solid-phase extraction procedure with polymeric mixed-mode cation exchange columns, the unstable analytes were protected by ascorbic acid, drying with nitrogen and exclusion of light. The limits of detection and quantitation for all analytes were low. Recovery was ≥86 % for all analytes and no significant matrix effects were observed. Interday and intraday imprecisions at different concentrations ranged from 1.1 to 8.2 % relative standard deviation, bias was within ±5.3 %. Processed samples were stable in the autosampler for at least 2 days. Furthermore, freeze/thaw and long-term stability were investigated. The method was successfully applied to authentic serum and urine samples.

  5. A New Indole Alkaloid from the Toad Venom of Bufo bufo gargarizans.

    Science.gov (United States)

    Dai, Ying-Hui; Shen, Bo; Xia, Ming-Yu; Wang, An-Dong; Chen, Yu-Lin; Liu, Dong-Chun; Wang, Dong

    2016-03-16

    A new indole alkaloid named bufobutarginine (1), along with three known bufotenines, namely, serotonin (2), bufotenidine (3), and bufotenine (4), were isolated from the water extract of toad venom. Their structures were elucidated by spectral methods. This is the first time that arginine has been found to be involved in the biosynthesis of bufotenines in parotid of toad. The cytotoxic activities of these compounds have been assayed against A375 and A549 cell lines by the MTT method; however, they showed no cytotoxic activities.

  6. N-methyl serotonin analogues from the Bufo bufo toad venom interact efficiently with the α7 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Kryukova, E V; Lebedev, D S; Ivanov, I A; Ivanov, D A; Starkov, V G; Tsetlin, V I; Utkin, Yu N

    2017-01-01

    Two low-molecular-weight compounds were isolated from the parotid gland secret of the toad Bufo bufo, which by absorption spectra and HPLC-MS/MS chromatography data correspond to di- and trimethyl derivatives of serotonin (5-hydorxytryptamine): bufotenine (confirmed by counter synthesis) and bufotenidine (5-HTQ). In experiments on competitive radioligand binding, these compounds showed a higher affinity and selectivity for neuronal α7 nicotinic acetylcholine receptors compared with the muscular cholinergic receptors. The most efficient compound in terms of binding value was bufotenine, the efficiency of 5-HTQ was an order of magnitude lower, and the minimal activity was exhibited by serotonin.

  7. Stimulus control by 5methoxy-N,N-dimethyltryptamine in wild-type and CYP2D6-humanized mice

    OpenAIRE

    Winter, J. C.; Amorosi, D. J.; Rice, Kenner C.; Cheng, Kejun; Yu, Ai-Ming

    2011-01-01

    In previous studies we have observed that, in comparison with wild type mice, Tg-CYP2D6 mice have increased serum levels of bufotenine [5-hydroxy-N,N-dimethyltryptamine] following the administration of 5-MeO-DMT. Furthermore, following the injection of 5-MeO-DMT, harmaline was observed to increase serum levels of bufotenine and 5-MeO-DMT in both wild-type and Tg-CYP2D6 mice. In the present investigation, 5-MeO-DMT-induced stimulus control was established in wild-type and Tg-CYP2D6 mice. The t...

  8. Stimulus control by 5-methoxy-N,N-dimethyltryptamine in wild-type and CYP2D6-humanized mice.

    Science.gov (United States)

    Winter, J C; Amorosi, D J; Rice, Kenner C; Cheng, Kejun; Yu, Ai-Ming

    2011-09-01

    In previous studies we have observed that, in comparison with wild type mice, Tg-CYP2D6 mice have increased serum levels of bufotenine [5-hydroxy-N,N-dimethyltryptamine] following the administration of 5-MeO-DMT. Furthermore, following the injection of 5-MeO-DMT, harmaline was observed to increase serum levels of bufotenine and 5-MeO-DMT in both wild-type and Tg-CYP2D6 mice. In the present investigation, 5-MeO-DMT-induced stimulus control was established in wild-type and Tg-CYP2D6 mice. The two groups did not differ in their rate of acquisition of stimulus control. When tested with bufotenine, no 5-MeO-DMT-appropriate responding was observed. In contrast, the more lipid soluble analog of bufotenine, acetylbufotenine, was followed by an intermediate level of responding. The combination of harmaline with 5-MeO-DMT yielded a statistically significant increase in 5-MeO-DMT-appropriate responding in Tg-CYP2D6 mice; a comparable increase occurred in wild-type mice. In addition, it was noted that harmaline alone was followed by a significant degree of 5-MeO-DMT-appropriate responding in Tg-CYP2D6 mice. It is concluded that wild-type and Tg-CYPD2D6 mice do not differ in terms of acquisition of stimulus control by 5-MeO-DMT or in their response to bufotenine and acetylbufotenine. In both groups of mice, harmaline was found to enhance the stimulus effects of 5-MeO-DMT. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Stimulus control by 5methoxy-N,N-dimethyltryptamine in wild-type and CYP2D6-humanized mice

    Science.gov (United States)

    Winter, J. C.; Amorosi, D. J.; Rice, Kenner C.; Cheng, Kejun; Yu, Ai-Ming

    2011-01-01

    In previous studies we have observed that, in comparison with wild type mice, Tg-CYP2D6 mice have increased serum levels of bufotenine [5-hydroxy-N,N-dimethyltryptamine] following the administration of 5-MeO-DMT. Furthermore, following the injection of 5-MeO-DMT, harmaline was observed to increase serum levels of bufotenine and 5-MeO-DMT in both wild-type and Tg-CYP2D6 mice. In the present investigation, 5-MeO-DMT-induced stimulus control was established in wild-type and Tg-CYP2D6 mice. The two groups did not differ in their rate of acquisition of stimulus control. When tested with bufotenine, no 5-MeO-DMT-appropriate responding was observed. In contrast, the more lipid soluble analog of bufotenine, acetylbufotenine, was followed by an intermediate level of responding. The combination of harmaline with 5-MeO-DMT yielded a statistically significant increase in 5-MeO-DMT-appropriate responding in Tg-CYP2D6 mice; a comparable increase occurred in wild-type mice. In addition, it was noted that harmaline alone was followed by a significant degree of 5-MeO-DMT-appropriate responding in Tg-CYP2D6 mice. It is concluded that wild-type and Tg-CYPD2D6 mice do not differ in terms of acquisition of stimulus control by 5-MeO-DMT or in their response to bufotenine and acetylbufotenine. In both groups of mice, harmaline was found to enhance the stimulus effects of 5-MeO-DMT. PMID:21624387

  10. Effects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-methoxy-N,N-dimethyltryptamine metabolism and pharmacokinetics.

    Science.gov (United States)

    Shen, Hong-Wu; Wu, Chao; Jiang, Xi-Ling; Yu, Ai-Ming

    2010-07-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural psychoactive indolealkylamine drug that has been used for recreational purpose. Our previous study revealed that polymorphic cytochrome P450 2D6 (CYP2D6) catalyzed 5-MeO-DMT O-demethylation to produce active metabolite bufotenine, while 5-MeO-DMT is mainly inactivated through deamination pathway mediated by monoamine oxidase (MAO). This study, therefore, aimed to investigate the impact of CYP2D6 genotype/phenotype status and MAO inhibitor (MAOI) on 5-MeO-DMT metabolism and pharmacokinetics. Enzyme kinetic studies using recombinant CYP2D6 allelic isozymes showed that CYP2D6.2 and CYP2D6.10 exhibited 2.6- and 40-fold lower catalytic efficiency (V(max)/K(m)), respectively, in producing bufotenine from 5-MeO-DMT, compared with wild-type CYP2D6.1. When co-incubated with MAOI pargyline, 5-MeO-DMT O-demethylation in 10 human liver microsomes showed significantly strong correlation with bufuralol 1'-hydroxylase activities (R(2)=0.98; P5-MeO-DMT depletion and increased bufotenine formation in human CYP2D6 extensive metabolizer hepatocytes. In vivo studies in wild-type and CYP2D6-humanized (Tg-CYP2D6) mouse models showed that Tg-CYP2D6 mice receiving the same dose of 5-MeO-DMT (20mg/kg, i.p.) had 60% higher systemic exposure to metabolite bufotenine. In addition, pretreatment of harmaline (5mg/kg, i.p.) led to 3.6- and 4.4-fold higher systemic exposure to 5-MeO-DMT (2mg/kg, i.p.), and 9.9- and 6.1-fold higher systemic exposure to bufotenine in Tg-CYP2D6 and wild-type mice, respectively. These findings indicate that MAOI largely affects 5-MeO-DMT metabolism and pharmacokinetics, as well as bufotenine formation that is mediated by CYP2D6. (c) 2010 Elsevier Inc. All rights reserved.

  11. Pharmacokinetic interactions between monoamine oxidase A inhibitor harmaline and 5-methoxy-N,N-dimethyltryptamine, and the impact of CYP2D6 status.

    Science.gov (United States)

    Jiang, Xi-Ling; Shen, Hong-Wu; Mager, Donald E; Yu, Ai-Ming

    2013-05-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT or street name "5-MEO") is a newer designer drug belonging to a group of naturally occurring indolealkylamines. Our recent study has demonstrated that coadministration of monoamine oxidase A (MAO-A) inhibitor harmaline (5 mg/kg) increases systemic exposure to 5-MeO-DMT (2 mg/kg) and active metabolite bufotenine. This study is aimed at delineating harmaline and 5-MeO-DMT pharmacokinetic (PK) interactions at multiple dose levels, as well as the impact of CYP2D6 that affects harmaline PK and determines 5-MeO-DMT O-demethylation to produce bufotenine. Our data revealed that inhibition of MAO-A-mediated metabolic elimination by harmaline (2, 5, and 15 mg/kg) led to a sharp increase in systemic and cerebral exposure to 5-MeO-DMT (2 and 10 mg/kg) at all dose combinations. A more pronounced effect on 5-MeO-DMT PK was associated with greater exposure to harmaline in wild-type mice than CYP2D6-humanized (Tg-CYP2D6) mice. Harmaline (5 mg/kg) also increased blood and brain bufotenine concentrations that were generally higher in Tg-CYP2D6 mice. Surprisingly, greater harmaline dose (15 mg/kg) reduced bufotenine levels. The in vivo inhibitory effect of harmaline on CYP2D6-catalyzed bufotenine formation was confirmed by in vitro study using purified CYP2D6. Given these findings, a unified PK model including the inhibition of MAO-A- and CYP2D6-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models. This PK model may be further employed to predict harmaline and 5-MeO-DMT PK interactions at various doses, define the impact of CYP2D6 status, and drive harmaline-5-MeO-DMT pharmacodynamics.

  12. LC-MS/MS quantitative determination of Tetrapterys mucronata alkaloids, a plant occasionally used in ayahuasca preparation.

    Science.gov (United States)

    Queiroz, M M F; Marti, G; Queiroz, E F; Marcourt, L; Castro-Gamboa, I; Bolzani, V S; Wolfender, J-L

    2015-01-01

    Tetrapterys mucronata Cav. (Malpighiaceae) is a plant used in some regions of Brazil in the preparation of ayahuasca. To determine the content of the main tryptamine alkaloids in the stem bark of T. mucronata Cav. and assess their possible toxic and hallucinogenic properties based on the doses found in a water decoction that mimics the ayahuasca preparation. Four alkaloids previously described for their toxic and hallucinogenic properties were quantitated by multiple reaction monitoring HPLC combined with electrospray ionisation and tandem MS (HPLC-ESI/MS/MS) in the water decoction and ethanolic extracts from the bark of T. mucronata. Exhaustive extraction of the stem barks with ethanol revealed the following alkaloid levels: bufotenine (1) 3.26 ± 0.31 mg/g, 5-methoxy-N-methyltryptamine (2) 0.88 ± 0.08 mg/g, 5-methoxy-bufotenine (3) 3.07 ± 0.22 mg/g and 2-methyl-6-methoxy-1,2,3,4-tetrahydro-β-carboline (4) 0.14 ± 0.004 mg/g. The water decoction presented slightly lower levels, ranging between 2.32 ± 0.14, 0.50 ± 0.04, 1.53 ± 0.09 and 0.10 ± 0.01 mg/g for (1), (2), (3) and (4) respectively. The HPLC-ESI/MS/MS quantitation revealed significant alkaloid levels, in particular for bufotenine and 5-methoxy-bufotenine. As such compounds are known for their toxic and hallucinogenic properties, these results indicate that the consumption of this plant as an ingredient in ayahuasca preparations may present a risk to consumers. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions.

    Science.gov (United States)

    Shen, Hong-Wu; Jiang, Xi-Ling; Winter, Jerrold C; Yu, Ai-Ming

    2010-10-01

    5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as a nonselective serotonin (5-HT) agonist and causes many physiological and behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) to an active metabolite, bufotenine, while it is mainly inactivated through the deamination pathway mediated by monoamine oxidase A (MAO-A). 5-MeO-DMT is often used with MAO-A inhibitors such as harmaline. Concurrent use of harmaline reduces 5-MeO-DMT deamination metabolism and leads to a prolonged and increased exposure to the parent drug 5-MeO-DMT, as well as the active metabolite bufotenine. Harmaline, 5-MeO-DMT and bufotenine act agonistically on serotonergic systems and may result in hyperserotonergic effects or serotonin toxicity. Interestingly, CYP2D6 also has important contribution to harmaline metabolism, and CYP2D6 genetic polymorphism may cause considerable variability in the metabolism, pharmacokinetics and dynamics of harmaline and its interaction with 5-MeO-DMT. Therefore, this review summarizes recent findings on biotransformation, pharmacokinetics, and pharmacological actions of 5-MeO-DMT. In addition, the pharmacokinetic and pharmacodynamic drug-drug interactions between harmaline and 5-MeO-DMT, potential involvement of CYP2D6 pharmacogenetics, and risks of 5-MeO-DMT intoxication are discussed.

  14. Drug: D06750 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06750 Crude ... Drug Toad venom (JP17) Hellebrin [CPD:C08868], Resibufogenin [CPD...:C17058], Cinobufagin [CPD:C16931], Bufalin [CPD:C16922], Bufotalin [CPD:C16923], Cinobufotalin [CPD:C16932], Gamabufo...C16921], Cardenolides, Bufotenine [CPD:C08299], Bufotenidine [CPD:C13664], Epiren...aginol, Marinobufagin, Resibufagin, Serotonine, Bufothionine, Dehydrobufotenine, Bufotoxin, Cholesterol [CPD...terol [CPD:C01694], Campesterol [CPD:C01789], Sitosterol [CPD:C01753] ... Bufo bufo gargagrizans [TAX:30331], Bufo

  15. Environ: E00121 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available E00121 Toad venom (JP17) Crude drug Hellebrin [CPD:C08868], Resibufogenin [CPD:C17...058], Cinobufagin [CPD:C16931], Bufalin [CPD:C16922], Bufotalin [CPD:C16923], Cinobufotalin [CPD:C16932], Gamabufo...talin [CPD:C16962], Telocinobufagin [CPD:C17072], Hellebrigenin [CPD:C16969], Bufadienolides [CPD:C16921], Cardenolides, Bufo...tenine [CPD:C08299], Bufotenidine [CPD:C13664], Epirenamin...ol, Marinobufagin, Resibufagin, Serotonine, Bufothionine, Dehydrobufotenine, Bufotoxin, Cholesterol [CPD:C00

  16. Environ: E00121 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available E00121 Toad venom (JP16) Crude drug Hellebrin [CPD:C08868], Resibufogenin [CPD:C170...58], Cinobufagin [CPD:C16931], Bufalin [CPD:C16922], Bufotalin [CPD:C16923], Cinobufotalin [CPD:C16932], Gamabufo...talin [CPD:C16962], Telocinobufagin [CPD:C17072], Hellebrigenin [CPD:C16969], Bufadienolides [CPD:C16921], Cardenolides, Bufo...tenine [CPD:C08299], Bufotenidine [CPD:C13664], Epirenamine...l, Marinobufagin, Resibufagin, Serotonine, Bufothionine, Dehydrobufotenine, Bufotoxin, Cholesterol [CPD:C001

  17. Pharmacokinetic Interactions between Monoamine Oxidase A Inhibitor Harmaline and 5-Methoxy-N,N-Dimethyltryptamine, and the Impact of CYP2D6 Status

    OpenAIRE

    Jiang, Xi-Ling; Shen, Hong-Wu; Mager, Donald E.; Yu, Ai-Ming

    2013-01-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT or street name “5-MEO”) is a newer designer drug belonging to a group of naturally occurring indolealkylamines. Our recent study has demonstrated that coadministration of monoamine oxidase A (MAO-A) inhibitor harmaline (5 mg/kg) increases systemic exposure to 5-MeO-DMT (2 mg/kg) and active metabolite bufotenine. This study is aimed at delineating harmaline and 5-MeO-DMT pharmacokinetic (PK) interactions at multiple dose levels, as well as the impact...

  18. Effects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-Methoxy-N,N-dimethyltryptamine Metabolism and Pharmacokinetics

    OpenAIRE

    Shen, Hong-Wu; Wu, Chao; Jiang, Xi-Ling; Yu, Ai-Ming

    2010-01-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural psychoactive indolealkylamine drug that has been used for recreational purpose. Our previous study revealed that polymorphic cytochrome P450 2D6 (CYP2D6) catalyzed 5-MeO-DMT O-demethylation to produce active metabolite bufotenine, while 5-MeO-DMT is mainly inactivated through deamination pathway mediated by monoamine oxidase (MAO). This study, therefore, aimed to investigate the impact of CYP2D6 genotype/phenotype status and MAO inhibi...

  19. Psychedelic 5-Methoxy-N,N-dimethyltryptamine: Metabolism, Pharmacokinetics, Drug Interactions, and Pharmacological Actions

    OpenAIRE

    Shen, Hong-Wu; Jiang, Xi-Ling; Winter, Jerrold C.; Yu, Ai-Ming

    2010-01-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as a nonselective serotonin (5-HT) agonist and causes many physiological and behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) to an active metabolite, bufotenine, while it is mainly inactivated through the deamination pathway mediated by monoamine oxidase A (MAO-A). 5-MeO-DMT is often used with MAO-A inhibitors such as h...

  20. Lack of bufadienolides in the skin secretion of red bellied toads, Melanophryniscus spp. (Anura, Bufonidae), from Uruguay.

    Science.gov (United States)

    Mebs, Dietrich; Wagner, Moritz G; Pogoda, Werner; Maneyro, Raul; Kwet, Axel; Kauert, Gerold

    2007-01-01

    The South-American red bellied toads (Melanophryniscus spp.) belonging to the Bufonidae family contain toxic alkaloids in their skin, predominantly of the pumiliotoxin group. Whole animal methanolic extracts of individual specimens of three species (Melanophryniscus atroluteus, M. devincenzii, and M. montevidensis) were analyzed for the presence of toad specific bufadienolides and indolalkylamines (serotonin derivatives) by HPLC-electrospray (ESI)-MS-TOF. No bufadienolides, but few bufotenines, mainly dehydrobufotenine, were detected in the extracts in variable amounts. The concentration of the dehydrobufotenine in the extracts seems to be species specific. Whereas M. atroluteus and M. montevidensis contain very low or trace amounts, M. devincenzii specimens exhibit high concentrations of this indolalkylamine. In comparison, analysis of extracts from Bufo arenarum (Uruguay) and from B. bufo (Germany) confirmed the presence of bufadienolides as well as of bufotenine derivatives. Tadpoles of both species exhibited a different pattern: extracts from B. arenarum tadpoles contained only dehydrobufotenine, but those from B. bufo tadpoles bufotoxin and two alkylamines. Melanophryniscus toads appear not to be able to compensate the high variability of toxic skin alkaloids by producing defensive bufadienolides.

  1. The relationship between poison frog chemical defenses and age, body size, and sex.

    Science.gov (United States)

    Jeckel, Adriana M; Saporito, Ralph A; Grant, Taran

    2015-01-01

    Amphibians secrete a wide diversity of chemicals from skin glands as defense against predators, parasites, and pathogens. Most defensive chemicals are produced endogenously through biosynthesis, but poison frogs sequester lipophilic alkaloids from dietary arthropods. Alkaloid composition varies greatly, even among conspecific individuals collected at the same time and place, with some individuals having only a few micrograms of one or a few alkaloids and others possessing >1 mg of >30 alkaloids. The paucity of alkaloids in juveniles and their abundance in adults suggests that alkaloids accumulate over time; however, alkaloid diversity is highly variable among adult poison frogs and has never been studied in relation to individual age. Using skeletochronology to infer individual ages and gas chromatography-mass spectrometry and vapor phase Fourier-transform infrared spectral analysis to identify the defensive chemicals of 63 individuals, we tested the relationship between defensive chemicals and age, size, and sex in the Brazilian red-belly toad, Melanophryniscus moreirae, a poison frog that possesses both sequestered alkaloids and the biosynthesized indolealkylamine bufotenine. Adult females were, on average, older and larger than adult males. Juveniles were smaller but not necessarily younger than adults and possessed bufotenine and 18 of the 37 alkaloids found in adults. Alkaloid richness was positively related to age, but not size, whereas the quantities of sequestered alkaloids and bufotenine were positively related to size, but not age. Defensive chemicals were unrelated to sex, independent of size. The relationship between alkaloid richness and age appears to result from the gradual accumulation of alkaloids over a frog's lifetime, whereas the relationship between the quantity of defensive chemicals and size appears to be due to the greater storage capacity of larger individuals. The decoupling of age and size effects increases the amount of individual

  2. Pharmepéna-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5-methoxy-N,N-dimethyl-tryptamine.

    Science.gov (United States)

    Ott, J

    2001-01-01

    Summarized are psychonautic bioassays (human self-experiments) of pharmepéna--crystalline 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; O-Me-bufotenine), at times combined with crystalline beta-carbolines (harmaline or harmine). These substances were administered via intranasal, sublingual and oral routes, by way of pharmacological modeling of diverse South American shamanic inebriants (principally the snuffs epéna/nyakwana, prepared from barks of diverse species of Virola.) Intranasal, sublingual and oral psychoactivity of 5-MeO-DMT, and the 1967 Holmstedt-Lindgren hypothesis of the paricá-effect--intranasal potentiation of tryptamines by concomitant administration of monoamine-oxidase-inhibiting (MAOI) beta-carbolines from stems of Banisteriopsis caapi admixed with the snuffs--have been confirmed by some 17 psychonautic bioassays. Salient phytochemical and psychonautic literature is reviewed.

  3. Psychoactive natural products: overview of recent developments

    Directory of Open Access Journals (Sweden)

    István Ujváry

    2014-03-01

    Full Text Available Natural psychoactive substances have fascinated the curious mind of shamans, artists, scholars and laymen since antiquity. During the twentieth century, the chemical composition of the most important psychoactive drugs, that is opium, cannabis, coca and "magic mushrooms", has been fully elucidated. The mode of action of the principal ingredients has also been deciphered at the molecular level. In the past two decades, the use of herbal drugs, such as kava, kratom and Salvia divinorum, began to spread beyond their traditional geographical and cultural boundaries. The aim of the present paper is to briefly summarize recent findings on the psychopharmacology of the most prominent psychoactive natural products. Current knowledge on a few lesser-known drugs, including bufotenine, glaucine, kava, betel, pituri, lettuce opium and kanna is also reviewed. In addition, selected cases of alleged natural (or semi-natural products are also mentioned.

  4. Behavioral and pharmacokinetic interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine.

    Science.gov (United States)

    Halberstadt, Adam L

    2016-04-01

    Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. We have shown previously that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The goal of the present studies was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation. The present studies examined whether an MAOI can alter the respective contributions of 5-HT1A and 5-HT2A receptors to the effects of 5-MeO-DMT on PPI. A series of interaction studies using the 5-HT1A antagonist WAY-100,635 and the 5-HT2A antagonist MDL 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in rats pretreated with an MAOI. The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using liquid chromatography-electrospray ionization-selective reaction monitoring-tandem mass spectrometry (LC-ESI-SRM-MS/MS). 5-MeO-DMT (1mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100,635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. The present results confirm that 5-MeO-DMT can disrupt PPI by

  5. 5-HT1C receptor-mediated stimulation of inositol phosphate production in pig choroid plexus. A pharmacological characterization.

    Science.gov (United States)

    Hoyer, D; Waeber, C; Schoeffter, P; Palacios, J M; Dravid, A

    1989-03-01

    1) 5-HT (5-hydroxytryptamine, serotonin) induces inositol phosphate production in a pig choroid plexus preparation. This effect has been pharmacologically characterized and the data compared to those obtained from radioligand binding studies performed with [3H]mesulergine to 5-HT1C sites in pig choroid plexus membranes. 2) The rank order of potency of agonists stimulating inositol phosphate production was: alpha-methyl-5-HT greater than 1-methyl-5-HT greater than DOI greater than bufotenine = SKF 83566 = 5-HT greater than 5-MeO-DMT greater than 5-MeOT = RU 24969 greater than SCH 23390 greater than 5-CT. 8-OH-DPAT was virtually devoid of activity at 100 mumol/l. 3) The increase in inositol phosphate production induced by 5-HT and other agonists was surmountably antagonised by mesulergine, ketanserin and spiperone with pKB values of 8.7, 6.7 and 5.3, respectively. 4) The rank order of potency of antagonists was: metergoline greater than mesulergine greater than LY 53857 greater than ritanserin greater than methiothepin greater than mianserin greater than cyproheptadine greater than pirenperone greater than cinanserin greater than ketanserin greater than spiperone. The following antagonists were virtually devoid of activity at 100 mumol/l; pindolol, 21-009 and yohimbine. 5) The results obtained both with agonists and antagonists strongly support the view that 5-HT1C receptors mediate agonist induced production of inositol phosphates in pig choroid plexus.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Plants and mushrooms of abuse.

    Science.gov (United States)

    Spoerke, D G; Hall, A H

    1990-08-01

    The plants described earlier are only a few of those that can be misused. Most have effects similar to those of more popular synthetic drugs but can cause unpleasant side effects and unpredictable results. Identification of the offending botanic agent can be problematic. These plants are still used because most are legal to possess, and they do produce desired hallucinogenic and stimulant effects. Because the active ingredients are similar pharmacologically to agents such as LSD and amphetamine, required treatment is often similar. The challenge for the Emergency Department physician is to recognize the potential for abuse of these botanic agents, their probable side effects, and the need for appropriate, usually supportive, treatment. There are many more plants with abuse potential than can be discussed in detail in an article of this size. Table 1 lists a number of other agents that might be misused. Phenylamine hallucinogens occur in several species and include N,N-dimethyltryptamine (DMT), N-monomethyltryptamine (MMT), 5-methoxy-N-N-dimethyltryptamine (5-MeO-DMT), 5-methoxy-N-monomethyltryptamine (5-MeO-DMT), 5-methoxy-N-monomethyltryptamine (5-MeO-MMT), 5-hydroxy-N-N-dimethyltryptamine (bufotenine or 5-H-DMT), and N,N-dimethyltryptamine-N-oxide (DMT-N-oxide).

  7. Artifactual high-affinity and saturable binding of (3H)5-hydroxytryptamine induced by radioligand oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Peroutka, S.J.; Ison, P.J.; Liu, D.U.; Barrett, R.W.

    1986-07-01

    The binding of (3H)5-hydroxytryptamine (5-HT, serotonin) to cerebellar membranes was examined after preincubation of (/sup 3/H)5-HT in the presence or absence of ascorbate. The tissue preparation was identical in all experiments and consisted of rat cerebellar homogenates in Tris-HCl buffer with 0.1% ascorbate. Cerebellar membranes were used because of their low density of 5-HT1 binding sites. In the presence of ascorbate during a 4-h preincubation period, minimal specific binding of 2 nM (/sup 3/H)5-HT is detected. Similar results are obtained with equimolar concentrations of other antioxidants (butylated hydroxytoluene, sodium dithionite, and sodium metabisulfite). Apparent specific binding increases 14-fold following a 4-h preincubation of (/sup 3/H)5-HT in the absence of ascorbate. The increase in apparent specific (/sup 3/H)5-HT binding is time-dependent and plateaus after 4-6 h of preincubation. When ascorbate is present during the 4-h preincubation, Scatchard analysis of (/sup 3/H)5-HT binding reveals a KD value of 3.0 +/- 0.3 nM and a Bmax value of 1.9 +/- 0.2 pmol/g tissue. When ascorbate is absent during the preincubation, the KD is essentially unchanged at 3.6 +/- 0.1 nM but the Bmax is significantly increased to 36.5 +/- 7 pmol/g tissue. Drug competition studies reveal that the apparent specific (/sup 3/H)5-HT binding in the absence of ascorbate appears to be displaced by nanomolar concentrations of hydroxylated tryptamines (5-HT, bufotenine) but not by nonhydroxylated tryptamines (5-methoxytryptamine, tryptamine). HPLC analysis demonstrates that (3H)5-HT is essentially destroyed by a 4-h incubation at 22/sup 0/C in the absence of ascorbate.

  8. Analysis of 44 drugs of abuse and metabolites in wastewater and river water using a hybrid quadrupole time-of-flight tandem mass spectrometry

    Science.gov (United States)

    Andres-Costa, M. Jesus; Andreu, Vicente; Picó, Yolanda

    2016-04-01

    The presence of drugs of abuse in the aquatic environment has been recognized as an important issue for the ecosystem due their possible negative effect on it (Richardson, 2011). Incomplete removal of these substances during wastewater treatment could be one of the causes of their release in the environment (Zuccato and Castiglioni, 2009). Pollution by illicit drug residues at very low concentrations is generalized in populated areas, with potential risks for human health and the environment (Zuccato, 2008; Castiglioni et al 2007).The aim of this study was to screen and quantify 44 drugs of abuse and metabolites of wastewater samples using a hybrid quadrupole time-of-flight tandem mass spectrometry and furthermore carry out a post-target screening to identify additional compounds present in the water samples. Wastewater samples were collected from the influent and effluent of three wastewater treatment plants (WWTPs) in Valencia and river water samples form Turia River Basin. Illicit drugs were extracted by solid-phase extraction (SPE). The chromatography was performed with an Agilent 1260 Infinity ultra high performance liquid chromatography (UHPLC). The UHPLC system was coupled to a hybrid quadrupole time-of-flight ABSciex Triple TOFTM 5600. All analytes were analyzed in positive mode. Acquiring full scan MS data was employed for quantification of drugs of abuse, and automatic data dependent information product ion spectra (IDA-MS/MS) was checked for identifying emerging illicit drugs and other compounds in water samples. The use of a database containing 1212 compounds achieved high confidence results for a wide number of contaminants. In the present study, the presence of compounds that belong to amphetamines group (amphetamine, methamphetamine, ephedrine, MDMA, MDA and MDEA), tryptamines (bufotenine), pirrolidinophenone group (α-PVP and 4'-MePHP), arylcyclohexylamines (ketamine), cocainics (cocaine, benzoylecgonine, cocaethylene and ecgonine methyl ester) and