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Sample records for bufotenine

  1. Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues.

    Science.gov (United States)

    Kärkkäinen, J; Forsström, T; Tornaeus, J; Wähälä, K; Kiuru, P; Honkanen, A; Stenman, U H; Turpeinen, U; Hesso, A

    2005-01-01

    Bufotenine and N,N-dimethyltryptamine (DMT) are hallucinogenic dimethylated indolethylamines (DMIAs) formed from serotonin and tryptamine by the enzyme indolethylamine N-methyltransferase (INMT) ubiquitously present in non-neural tissues. In mammals, endogenous bufotenine and DMT have been identified only in human urine. The DMIAs bind effectively to 5HT receptors and their administration causes a variety of autonomic effects, which may reflect their actual physiological function. Endogenous levels of bufotenine and DMT in blood and a number of animal and human tissues were determined using highly sensitive and specific quantitative mass spectrometric techniques. A new finding was the detection of large amounts of bufotenine in stools, which may be an indication of its role in intestinal function. It is suggested that fecal and urinary bufotenine originate from epithelial cells of the intestine and the kidney, respectively, although the possibility of their synthesis by intestinal bacteria cannot be excluded. Only small amounts of the DMIAs were found in somatic or neural tissues and none in blood. This can be explained by rapid catabolism of the DMIAs by mitochondrial monoamino-oxidase or by the fact that the dimethylated products of serotonin and tryptamine are not formed in significant amounts in most mammalian tissues despite the widespread presence of INMT in tissues. PMID:16095048

  2. Concise synthesis of N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine starting with bufotenine from Brazilian Anadenanthera ssp..

    Science.gov (United States)

    Moreira, Leandro A; Murta, Maria M; Gatto, Claudia C; Fagg, Christopher W; dos Santos, Maria L

    2015-04-01

    Bufotenine (1, 5-hydroxy-N,N-dimethyltryptamine) was isolated from seeds of Anadenanthera spp., a tree widespread in the Brazilian cerrado, using an efficient acid-base shakeout protocol. The conversion of bufotenine into N,N-dimethyltryptamine (4) and 5-methoxy-N,N-dimethyltryptamine (5) was accomplished through an innovative and short approach featuring the use of novel bufotenine-aminoborane complex (7). Furthermore, an easy methodology for conversion of bufotenine into 5-hydroxy-N,N,N-trimethyltryptamine (6) was well-established. This is the first study that highlights bufotenine as a resource for the production of N,N-dimethyltryptamines for either pharmacological and toxicological investigations or for synthetic purposes. PMID:25973481

  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. 75 FR 36693 - Importer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2010-06-28

    ..., 2010, and published in the Federal Register on March 24, 2010 (75 FR 14188), Sigma Aldrich... Bufotenine (7433) I Diethyltryptamine (7434) I Dimethyltryptamine (7435) I Psilocybin (7437) I Psilocyn...

  5. 77 FR 52366 - Manufacturer of Controlled Substances; Notice of Application; Cerilliant Corporation

    Science.gov (United States)

    2012-08-29

    ...-Methoxyamphetamine (7411) I 5-Methoxy-N-N-dimethyltryptamine (7431).... I Alpha-methyltryptamine (7432) I Bufotenine (7433) I Diethyltryptamine (7434) I Dimethyltryptamine (7435) I Psilocybin (7437) I Psilocyn (7438) I...

  6. 77 FR 2321 - Manufacturer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2012-01-17

    ...-Methoxyamphetamine (7411) I 5-Methoxy-N-N-dimethyltryptamine (7431)..... I Alpha-methyltryptamine (7432) I Bufotenine (7433) I Diethyltryptamine (7434) I Dimethyltryptamine (7435) I Psilocybin (7437) I Psilocyn (7438) I...

  7. 78 FR 54914 - Importer of Controlled Substances; Notice of Registration; Lipomed, Inc.

    Science.gov (United States)

    2013-09-06

    ... dated June 7, 2013, and published in the Federal Register on June 18, 2013, 78 FR 36591, Lipomed, Inc...-dimethyltryptamine (7431)..... I Alpha-methyltryptamine (7432) I Bufotenine (7433) I Psilocybin (7437) I...

  8. 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...

  9. 78 FR 54919 - Manufacturer of Controlled Substances; Notice of Registration; Alltech Associates, Inc.

    Science.gov (United States)

    2013-09-06

    ..., Inc. By Notice dated May 14, 2013 and published in the Federal Register on May 22, 2013, 78 FR 30331...-Methoxyamphetamine (7411) I 5-Methoxy-N-N-dimethyltryptamine (7431) I Alpha-methyltryptamine (7432) I Bufotenine (7433) I Diethyltryptamine (7434) I Dimethyltryptamine (7435) I Psilocybin (7437) I Psilocyn (7438) I...

  10. Chemical and enzymatic oxidative coupling of 5-hydroxy-N,N-dimethyltryptamine with amines.

    Science.gov (United States)

    Babin, F; Huynh-Dinh, T

    1987-07-01

    As part of a program aiming to obtain a covalent labeling of serotoninergic receptors we have studied the oxidative coupling of serotonin derivatives with amino compounds. The oxidation of bufotenine (2) by MnO2 and human ceruloplasmin followed by the Michael type addition with dansylcadaverine and dansyllysine gave a fluorescent adduct identified as fused oxazole structure 4. PMID:3599029

  11. 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

  12. 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. PMID:21624387

  13. 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. PMID:23393220

  14. 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; P<0.0001) and CYP2D6 contents (R(2)=0.77; P=0.0007), whereas no appreciable correlations with enzymatic activities of other P450 enzymes. Furthermore, concurrent MAOI harmaline sharply reduced 5-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. PMID:20206139

  15. 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. PMID:20942780

  16. 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...

  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. Drug: D06750 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06750 Crude, Drug Toad venom (JP16) 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

  20. 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

  1. A comparison of N,N-dimethyltryptamine, harmaline, and selected congeners in rats trained with LSD as a discriminative stimulus.

    Science.gov (United States)

    Helsley, S; Fiorella, D; Rabin, R A; Winter, J C

    1998-05-01

    1. A series of N-substituted tryptamines was compared with a series of beta-carbolines in rats trained to discriminate LSD (0.1 mg/kg) from saline. 2. Intermediate levels of substitution were elicited by MDMT (76.4%), DMT (77.9%), and DET (48.7%). 6-F-DET produced 41.3% LSD-appropriate responding at a dose of 6.0 mg/kg but only 4 of 8 subjects completed the test session thus precluding statistical analysis. Bufotenine (25.8%) also failed to substitute. Although none of the tryptamines substituted completely for LSD, the pattern of substitution is consonant with what is known of their activity in humans. MDMT, DMT, and DET are well established in the literature as hallucinogens but the same cannot be said for 6-F-DET and bufotenine. 3. Of the beta-carbolines tested, none substituted for LSD completely and only harmane elicited intermediate substitution (49.5%). No significant generalization of the LSD stimulus to 6-methoxyharmalan, harmaline, or THBC was observed. Thus, in contrast to the tryptamines, scant ability to substitute for LSD was observed in the beta-carbolines tested. 4. Taken together, the present data indicate that the representative tryptamines employed in the present study exhibit greater similarity to the LSD stimulus than do representative beta-carbolines. The receptor interactions responsible for these differences remain to be determined. PMID:9682278

  2. 11C-labeling of indolealkylamine alkaloids and the comparative study of their tissue distributions

    International Nuclear Information System (INIS)

    Five indolealkylamines (N,N-dimethyltryptamine, N-methyltryptamine, bufotenine, O-methylbufotenine, N,N,N-trimethyltryptamine iodide) were labeled with 11C by use of 11CH3I. The labeled compounds were synthesized with a radiochemical yield of 2-50% (based on trapped 11CH3I) in 20-35 min with radiochemical purities of more than 92%. The tissue distributions of these labeled compounds were investigated in rats. In all cases, the accumulations in the liver, lung and small intestine were high. [11C]DMT and [11C]OMB also accumulated to a large extent in the brain, where their accumulation was retained. Brain uptake of three other radiopharmaceuticals was low. [11C]DMT is the radiopharmaceutical of choice for the study of the serotonin action mechanism in the brain, because it has the highest radiochemical yield and the highest brain uptake of these 11C-labeled compounds. (author)

  3. Distribution of the hallucinogens N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine in rat brain following intraperitoneal injection: application of a new solid-phase extraction LC-APcI-MS-MS-isotope dilution method.

    Science.gov (United States)

    Barker, S A; Littlefield-Chabaud, M A; David, C

    2001-02-10

    A method for the solid-phase extraction (SPE) and liquid chromatographic-atmospheric pressure chemical ionization-mass spectrometric-mass spectrometric-isotope dilution (LC-APcI-MS-MS-ID) analysis of the indole hallucinogens N,N-dimethyltryptamine (DMT) and 5-methoxy DMT (or O-methyl bufotenin, OMB) from rat brain tissue is reported. Rats were administered DMT or OMB by the intraperitoneal route at a dose of 5 mg/kg and sacrificed 15 min post treatment. Brains were dissected into discrete areas and analyzed by the methods described as a demonstration of the procedure's applicability. The synthesis and use of two new deuterated internal standards for these purposes are also reported. PMID:11232854

  4. 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.

  5. Desmodeleganine, a new alkaloid from the leaves of Desmodium elegans as a potential monoamine oxidase inhibitor.

    Science.gov (United States)

    Zhi, Kang-Kang; Yang, Zhong-Duo; Shi, Dan-Feng; Yao, Xiao-Jun; Wang, Ming-Gang

    2014-10-01

    Desmodeleganine (1), a new potential monoamine oxidase inhibitor, along with three known alkaloids, bufotenin (2), hydroxy-N, N-dimethyltryptamine N(12)-oxide (3), 2-(5-methoxy-1H-indol-3-yl)-N, and N-dimethylethylamine (4) were isolated from the leaves of Desmodium elegans. Their structures were elucidated by IR, MS, 1D and 2D NMR spectra. 1 showed strong monoamine oxidase inhibitory activity with IC50 value of 13.92 ± 1.5 μM, when the IC50 value of iproniazid as a standard was 6.5 ± 0.5 μM. The molecular modeling was also performed to explore the binding mode of compounds 1, 2 at the active site of MAO-A and MAO-B. PMID:25102471

  6. 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

  7. Ayahoasca: an experimental psychosis that mirrors the transmethylation hypothesis of schizophrenia.

    Science.gov (United States)

    Pomilio, A B; Vitale, A A; Ciprian-Ollivier, J; Cetkovich-Bakmas, M; Gómez, R; Vázquez, G

    1999-04-01

    The experimental psychosis observed after drinking Ayahoasca, a South American hallucinogenic beverage from the Amazon Indians, reproduces the pathologic transmethylation theory of schizophrenia. This theory postulates a decrease in the monoamine oxidase (MAO) activity, which results in the accumulation of methylated indolealkylamines, such as bufotenin (5-hydroxy-N,N-dimethyltryptamine), N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine. These substances are strong hallucinogens as has been previously confirmed experimentally. On the other hand, it is known that Ayahoasca is a beverage usually prepared by boiling two plants, one of them rich in beta-carbolines, which are naturally occurring strong inhibitors of MAO, and the other with high quantities of DMT. This particular combination reproduces what is supposed to occur under pathologic conditions of different psychoses. The effects of Ayahoasca were studied in subjects, assessing urine levels of DMT by gas chromatography-mass spectrometry (GC-MS) before and after the intake of the beverage. The results of this study confirm that the hallucinogenic compounds detected in the healthy subjects' (post-Hoasca, but not before) urine samples are the same as those found in samples from acute psychotic unmedicated patients. The chemical composition of the Ayahoasca beverage, and of the plant material used for its preparation are also reported as well as psychometric and neuroendocrine subject parameters. PMID:10350367

  8. Citrus genus plants contain N-methylated tryptamine derivatives and their 5-hydroxylated forms.

    Science.gov (United States)

    Servillo, Luigi; Giovane, Alfonso; Balestrieri, Maria Luisa; Casale, Rosario; Cautela, Domenico; Castaldo, Domenico

    2013-05-29

    The occurrence and distribution in Citrus genus plants of N-methylated derivatives of tryptamine and their 5-hydroxylated forms are reported. Tryptamine, N-methyltryptamine, N,N-dimethyltryptamine, N,N,N-trimethyltryptamine, 5-hydroxytryptamine (serotonin), 5-hydroxy-N-methyltryptamine, 5-hydroxy-N,N-dimethyltryptamine (bufotenine), and 5-hydroxy-N,N,N-trimethyltryptamine (bufotenidine) were quantitated by LC-ESI-MS/MS. Leaves of all citrus plants examined contained N,N,N-trimethyltryptamine, a compound that we first discovered in the bergamot plant. Interestingly, we also found out that all plants examined contained 5-hydroxy-N,N-dimethyltryptamine and 5-hydroxy-N,N,N-trimethyltryptamine, compounds never described so far in the Citrus genus. As N,N,N-trimethyltryptamine and 5-hydroxy-N,N,N-trimethyltryptamine possess nicotine-like activity by exerting their action on acetylcholine receptors, it is conceivable that both represent the arrival point of a biosynthetic pathway aimed to provide Citrus plants with chemical defense against aggressors. This hypothesis is supported by our finding that leaves and seeds, which are more frequently attacked by biotic agents, are the parts of the plant where the highest levels of those compounds were found. PMID:23682903

  9. A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010.

    Science.gov (United States)

    Barker, Steven A; McIlhenny, Ethan H; Strassman, Rick

    2012-01-01

    Three indole alkaloids that possess differing degrees of psychotropic/psychedelic activity have been reported as endogenous substances in humans; N,N-dimethyltryptamine (DMT), 5-hydroxy-DMT (bufotenine, HDMT), and 5-methoxy-DMT (MDMT). We have undertaken a critical review of 69 published studies reporting the detection or detection and quantitation of these compounds in human body fluids. In reviewing this literature, we address the methods applied and the criteria used in the determination of the presence of DMT, MDMT, and HDMT. The review provides a historical perspective of the research conducted from 1955 to 2010, summarizing the findings for the individual compounds in blood, urine, and/or cerebrospinal fluid. A critique of the data is offered that addresses the strengths and weaknesses of the methods and approaches to date. The review also discusses the shortcomings of the existing data in light of more recent findings and how these may be overcome. Suggestions for the future directions of endogenous psychedelics research are offered. PMID:22371425

  10. 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.

  11. Simultaneous determination of traditional and emerging illicit drugs in sediments, sludges and particulate matter.

    Science.gov (United States)

    Álvarez-Ruiz, Rodrigo; Andrés-Costa, María Jesús; Andreu, Vicente; Picó, Yolanda

    2015-07-31

    An analytical method for determining traditional and emerging drugs of abuse in particulate matter, sewage sludge and sediment has been developed and validated. A total of 41 drugs of abuse and metabolites including cocainics, tryptamines, amphetamines, arylcyclohexylamines, cathinones, morphine derivatives, pyrrolidifenones derivatives, entactogens, piperazines and other psychostimulants were selected. Samples were ultrasound extracted with McIlvaine buffer and methanol, and the extracts were cleaned up by solid phase extraction (SPE) using Strata-X cartridges. Drugs were eluted using methanol and methanol-dichloromethane and determined by liquid chromatography tandem mass spectrometry. The optimum solid-liquid extraction (SLE) conditions were: weight 1g of sample and ultrasound assisted extraction (UAE) with 10mL of methanol-McIlvain buffer (1:1, v/v, pH 4.5) for 10min. Recoveries for all compounds were ≥50% in the three matrices with the exception of ephedrine (EPHE), 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), ecgonine methyester (ECME), heroin (HER), 3,4-methylendioxyamphetamine (MDA) and 4-acetoxy N,N'-dimethyltryptamine (4-AcO-DIPT) and methadone (MET). Data acquisition was done by selective reaction monitoring (SRM), and the two most abundant product ions were used for confirmation. Limits of detection were lower than 1.32ngg(-1) dry weight (d.w.) and limits of quantification were between 0.12 and 3.96ngg(-1) (d.w.). The method was applied to the analysis of particulate matter, where cocaine (COC), benzoylecgonine (BECG), ecgoninemethylester (ECME), cocaethylene (COCET), methadone (MET) and codeine (COD) were mostly detected. In the case of dehydrated sludge, opioids are at higher concentration than cocainics and some emerging drugs such as 4-methoxyamphetamine (PMA), ketamine (KET) and bufotenine (BUF) were detected. In sediment COC, 4-methoxyphencyclidine (4-MeO-PCP), MET and BECG were most relevant compounds. PMID:26091784

  12. Serotonin receptor subtype mediation of the interoceptive discriminative stimuli induced by 5-methoxy-N,N-dimethyltryptamine.

    Science.gov (United States)

    Spencer, D G; Glaser, T; Traber, J

    1987-01-01

    Male Wistar rats were trained to discriminate the interoceptive effects of 5-methoxy-N,N-dimethyltryptamine (5-OMe-DMT; 1.25 mg/kg, IP) from saline in a two-lever operant chamber. Following discrimination learning, the following drugs (with ED50 dose in mg/kg IP) dose-dependently generalized: lysergic acid diethylamide (LSD, 0.04), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.11), 6-methoxy-4-(dipropyl-amino)-1,3,4,5-tetrahydrobenz(c,d)indole hydrochloride (BAY R 1531, 0.15), 5-OMe-DMT itself (0.63), ipsapirone (TVX Q 7821, 2.7), and buspirone (3.8). The potencies of these drugs in generalization tests were best correlated with their binding affinities for the 5-HT1A serotonin receptor subtype (as measured by displacement of 3H-ipsapirone in the hippocampus). Drugs not, or only partially generalizing included quipazine, bufotenin, m-trifluoromethylphenylpiperazine (TFMPP), 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole succinate (RU 24969), citalopram, clomipramine, 1,4-dihydro-2,6-dimethyl-3-nitro-4(2-trifluoromethylphenyl)-pyridine-5- carboxylate (BAY K 8644), the buspirone metabolite 1-pyrimidinyl-piperazine (1-PP), methysergide, metergoline, and metitepine. Of the last three compounds with antagonistic activity at 5-HT receptors, as well as ketanserin, pizotifen, and ritanserin, only metitepine and pindolol could fully block the 5-OMe-DMT stimulus. Pizotifen blocked the generalization of quipazine fully, that of 5-OMe-DMT only partially, and that of ipsapirone not at all. These data indicate that the 5-HT1A receptor subtype is strongly involved in the transduction of the interoceptive discriminative stimuli induced by 5-OMe-DMT, with 5-HT2 agonism also playing a possible role. PMID:3122248

  13. 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