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Mitragynine

PubChem CID
3034396
Structure
Mitragynine_small.png
Mitragynine_3D_Structure.png
Molecular Formula
Synonyms
  • MITRAGYNINE
  • 4098-40-2
  • (-)-Mitragynine
  • Skf 12711
  • Mitragynin
Molecular Weight
398.5 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-06-24
  • Modify:
    2025-01-18
Description
Mitragynine is a monoterpenoid indole alkaloid.
Mitragynine has been reported in Mitragyna speciosa with data available.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Mitragynine.png

1.2 3D Conformer

1.3 Crystal Structures

COD records with this CID as component

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

methyl (E)-2-[(2S,3S,12bS)-3-ethyl-8-methoxy-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizin-2-yl]-3-methoxyprop-2-enoate
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C23H30N2O4/c1-5-14-12-25-10-9-15-21-18(7-6-8-20(21)28-3)24-22(15)19(25)11-16(14)17(13-27-2)23(26)29-4/h6-8,13-14,16,19,24H,5,9-12H2,1-4H3/b17-13+/t14-,16+,19+/m1/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

LELBFTMXCIIKKX-QVRQZEMUSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CC[C@@H]1CN2CCC3=C([C@@H]2C[C@@H]1/C(=C\OC)/C(=O)OC)NC4=C3C(=CC=C4)OC
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C23H30N2O4
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

6202-22-8

2.3.2 Deprecated CAS

1383-32-0, 6202-22-8

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DSSTox Substance ID

2.3.8 HMDB ID

2.3.9 KEGG ID

2.3.10 Metabolomics Workbench ID

2.3.11 Nikkaji Number

2.3.12 Wikidata

2.3.13 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 16,17-didehydro-9,17-dimethoxy-17,18-seco-20-alpha-yohimban-16-carboxylic acid methyl ester
  • kratom alkaloids
  • mitragynine
  • mitragynine ethanedisulfonate
  • mitragynine monohydrochloride
  • mitragynine, (16E)-isomer
  • mitragynine, (3beta,16E)-isomer
  • mitragynine, (3beta,16E,20beta)-isomer
  • SK and F 12711
  • SK and F-12711
  • SKF 12711

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
398.5 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
3.4
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
6
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
398.22055744 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
398.22055744 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
63.8 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
29
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
624
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
3
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Color / Form

White amorphous powder
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1073

3.2.2 Boiling Point

235 °C at 5 mm Hg
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-380

3.2.3 Melting Point

104 °C
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-380

3.2.4 Solubility

Soluble in alcohol, chloroform, acetic acid
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1073

3.2.5 Optical Rotation

Specific optical rotation: +39 deg at 25 °C/D (chloroform)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1073

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 GC-MS

Technique
GC/MS
Source of Spectrum
H.H.Maurer, M.Meyer, K.Pfleger, A.A. Weber / University of Saarland, D-66424 Homburg Germany
Copyright
Copyright © 2023-2024 Wiley-VCH GmbH. All Rights Reserved.
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4.1.2 MS-MS

1 of 6
View All
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

174.09241 100

226.14505 37.80

238.14587 34.50

399.22882 18.40

110.09757 17.20

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Spectra ID
Ionization Mode
Positive
Top 5 Peaks

159.06828 100

174.09233 57.46

144.08147 29.03

143.07457 22.42

117.07032 19.82

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4.1.3 LC-MS

1 of 14
View All
Authors
Tetsuya Mori, Center for Sustainable Resource Science, RIKEN
Instrument
LC, Waters Acquity UPLC System; MS, Waters Xevo G2 Q-Tof
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
6V
Column Name
Acquity bridged ethyl hybrid C18 (1.7 um, 2.1 mm * 100 mm, Waters)
Retention Time
5.539417
Precursor m/z
399.2278339
Precursor Adduct
[M+H]+
Top 5 Peaks

399.22916 999

174.09209 175

226.145 84

238.14507 73

110.09666 31

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License
CC BY-NC-SA
Reference
Tsugawa H., Nakabayashi R., Mori T., Yamada Y., Takahashi M., Rai A., Sugiyama R., Yamamoto H., Nakaya T., Yamazaki M., Kooke R., Bac-Molenaar JA., Oztolan-Erol N., Keurentjes JJB., Arita M., Saito K. (2019) "A cheminformatics approach to characterize metabolomes in stable-isotope-labeled organisms" Nature Methods 16(4):295-298. [doi:10.1038/s41592-019-0358-2]
2 of 14
View All
Authors
Tetsuya Mori, Center for Sustainable Resource Science, RIKEN
Instrument
LC, Waters Acquity UPLC System; MS, Waters Xevo G2 Q-Tof
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
6V
Column Name
Acquity bridged ethyl hybrid C18 (1.7 um, 2.1 mm * 100 mm, Waters)
Retention Time
5.539417
Precursor m/z
399.2278339
Precursor Adduct
[M+H]+
Top 5 Peaks

399.2283 999

399.28589 31

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License
CC BY-NC-SA
Reference
Tsugawa H., Nakabayashi R., Mori T., Yamada Y., Takahashi M., Rai A., Sugiyama R., Yamamoto H., Nakaya T., Yamazaki M., Kooke R., Bac-Molenaar JA., Oztolan-Erol N., Keurentjes JJB., Arita M., Saito K. (2019) "A cheminformatics approach to characterize metabolomes in stable-isotope-labeled organisms" Nature Methods 16(4):295-298. [doi:10.1038/s41592-019-0358-2]

4.1.4 Other MS

1 of 2
MS Category
Experimental
MS Type
Other
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
399.24
Instrument
Orbitrap
Ionization Mode
positive
Top 5 Peaks

399.240784 100

174.097046 49.39

400.243805 26.89

226.151154 17.38

238.151474 15.08

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2 of 2
MS Category
Experimental
MS Type
Other
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
399.24
Instrument
Orbitrap
Ionization Mode
positive
Top 5 Peaks

399.240784 100

174.097046 49.39

400.243805 26.89

226.151154 17.38

238.151474 15.08

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4.2 UV Spectra

UV max: 226, 292 nm (epsilon 41, 150, 660)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1073

4.3 IR Spectra

4.3.1 FTIR Spectra

Instrument Name
Bio-Rad FTS
Technique
KBr0
Source of Spectrum
Forensic Spectral Research
Source of Sample
Cayman Chemical Company
Catalog Number
<a href=https://www.caymanchem.com/product/11151>11151</a>
Lot Number
0467235-2
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.3.2 ATR-IR Spectra

Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Cayman Chemical Company
Catalog Number
<a href=https://www.caymanchem.com/product/11151>11151</a>
Lot Number
0467235-2
Copyright
Copyright © 2014-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4 Raman Spectra

Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Cayman Chemical Company
Catalog Number
<a href=https://www.caymanchem.com/product/11151>11151</a>
Lot Number
0467235-2
Copyright
Copyright © 2015-2024 John Wiley & Sons, Inc. All Rights Reserved.
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6 Chemical Vendors

7 Pharmacology and Biochemistry

7.1 Absorption, Distribution and Excretion

... LC-MS/MS analysis... was applied to quantify mitragynine in plasma samples of rats (n=8 per sampling time) treated with a single oral dose of 20 mg/kg. The following pharmacokinetic parameters were obtained (mean): maximum plasma concentration: 424 ng/mL; time to reach maximum plasma concentration: 1.26 hr; elimination half-life: 3.85 hr, apparent total clearance: 6.35 L/hr/kg, and apparent volume of distribution: 37.90 L/kg.
de Moraes NV et al; J Chromatog B Analyt Technol Biomed Life Sci 877 (24): 2593-7 (2009)

7.2 Metabolism / Metabolites

Mitragyna speciosa (Kratom) is ... a drug of abuse. When monitoring its abuse in urine, several alkaloids and their metabolites must be considered. In former studies, mitragynine (MG), its diastereomer speciogynine (SG), and paynantheine and their metabolites could be identified in rat and human urine using /Liquid Chromatography - Tandem Mass Spectometry/ (LC-MS(n)). In Kratom users' urines, besides MG and SG, further isomeric compounds were detected. To elucidate whether the MG and SG diastereomer speciociliatine (SC) and its metabolites represent further compounds, the phase I and II metabolites of SC were identified first in rat urine after the administration of the pure alkaloid. Then, the identified rat metabolites were screened for in the urine of Kratom users using the above-mentioned LC-MS(n) procedure. Considering the mass spectra and retention times, it could be confirmed that SC and its metabolites are so far the unidentified isomers in human urine. In conclusion, SC and its metabolites can be used as further markers for Kratom use, especially by consumption of raw material or products that contain a high amount of fruits of the Malaysian plant M. speciosa.
Philipp AA et al; Anal Bioanal Chem 399 (8): 2747-53 (2011)
... The aim of /this/ study is to identify the phase I and II metabolites of mitragynine (MG) in rat and human urine after solid-phase extraction (SPE) using liquid chromatography-linear ion trap mass spectrometry providing detailed structure information in the MSn mode particularly with high resolution. The seven identified phase I metabolites indicated that MG was metabolized by hydrolysis of the methylester in position 16, O-demethylation of the 9-methoxy group and of the 17-methoxy group, followed, via the intermediate aldehydes, by oxidation to carboxylic acids or reduction to alcohols and combinations of some steps. In rats, four metabolites were additionally conjugated to glucuronides and one to sulfate, but in humans, three metabolites to glucuronides and three to sulfates.
Philipp AA et al; J Mass Spectrom 44 (8): 1249-61 (2009)
During studies on the main Kratom alkaloid mitragynine (MG) in rats and humans, several dehydro analogs could be detected in urine of Kratom users, which were not found in rat urine after administration of pure MG. Questions arose as to whether these compounds are formed from MG only by humans or whether they are metabolites formed from the second abundant Kratom alkaloid paynantheine (PAY), the dehydro analog of MG. Therefore, the aim of /this/ study was to identify the phase I and II metabolites of PAY in rat urine after administration of the pure alkaloid. This was first isolated from Kratom leaves. Liquid chromatography-linear ion trap mass spectrometry provided detailed structure information of the metabolites in the MS(n) mode particularly with high resolution. Besides PAY, the following phase I metabolites could be identified: 9-O-demethyl PAY, 16-carboxy PAY, 9-O-demethyl-16-carboxy PAY, 17-O-demethyl PAY, 17-O-demethyl-16,17-dihydro PAY, 9,17-O-bisdemethyl PAY, 9,17-O-bisdemethyl-16,17-dihydro PAY, 17-carboxy-16,17-dihydro PAY, and 9-O-demethyl-17-carboxy-16,17-dihydro PAY. These metabolites indicated that PAY was metabolized via the same pathways as MG. Several metabolites were excreted as glucuronides or sulfates. The metabolism studies in rats showed that PAY and its metabolites corresponded to the MG-related dehydro compounds detected in urine of the Kratom users. In conclusion, PAY and its metabolites may be further markers for a Kratom abuse in addition of MG and its metabolites.
Philipp AA et al; Anal Bioanal Chem 396 (7): 2379-91 (2010)

7.3 Mechanism of Action

... Mitragynine (MIT), a mu-opioid agonist with antinociceptive and antitussive properties...
de Moraes NV et al; J Chromatog B Analyt Technol Biomed Life Sci 877 (24): 2593-7 (2009)
Mitragynine, the major alkaloid identified from Kratom, has been reported as a partial opioid agonist producing similar effects to morphine. An interesting minor alkaloid of Kratom, 7-hydroxymitragynine, has been reported to be more potent than morphine. Both Kratom alkaloids are reported to activate supraspinal mu- and delta- opioid receptors, explaining their use by chronic narcotics users to ameliorate opioid withdrawal symptoms.
Babu KM et al; Clon Toxicol (Phila) 46 (2): 146-52 (2008)

7.4 Human Metabolite Information

7.4.1 Cellular Locations

Membrane

8 Use and Manufacturing

8.1 Uses

The Thai medicinal plant Mitragyna speciosa (kratom) is misused as a herbal drug. Besides this, a new herbal blend has appeared on the drugs of abuse market, named Krypton, a mixture of O-demethyltramadol (ODT) and kratom. /Kratom/
Phillipp AA et al; Anal Bioanal Chem 400(1): 127-35 (2011)

8.2 Formulations / Preparations

Kratom
DEA; Selected Intelligence Brief: Herbal Drug Update: Kratom. In: Microgram Bulletin 38 (7): 114 (July 2005)

8.3 General Manufacturing Information

Mitragyna speciosa is a member of the Rubiaceae (coffee) family, and is indigenous to southeast Asia, notably in Thailand and Malaysia. Kratom is the original, common name used in Thailand ... but Mitragyna speciosa has at least half a dozen other common names (e.g., it is known as "Biak-Biak" in Malaysia.
DEA; Special Intelligence Brief - Kratom (Mitragyna speciosa). In: Microgram Bulletin (March 2006). Available from, as of March 18, 2011: https://www.justice.gov/dea/programs/forensicsci/microgram/mg0306/mg0306.html
More than 20 alkaloids have been identified in Kratom by various researchers; the most abundant is mitragynine, an indole alkaloin. /One study/ reported 66.2% mitragynine in the crude base extract of young Kratom leaves from Thailand. ... Several analogues of mitragynine, namely paynantheine, speciogynine, speciociliatine, and 7-alpha-hydroxy-7H-mitragynine, are also found in Kratom extracts. Analysis of a methanol extract with GC/MSD identified both mitragynine and another alkaloid, rhynchophylline.
DEA; Special Intelligence Brief - Kratom (Mitragyna speciosa). In: Microgram Bulletin (March 2006). Available from, as of March 18, 2011: https://www.justice.gov/dea/programs/forensicsci/microgram/mg0306/mg0306.html
... has been used by natives of Thailand and other regions of Southeast Asia as an herbal drug for decades ... provide energy and relief from muscle strains ... to substitute for opium when opium is not available. It has also been used to manage opiod withdrawal symptoms by chronic opiod users. /Kratom/
DEA; Drugs and Chemicals of Concern. Kratom (Mitragyna speciosa Korth). Dec 2010. US Dept Justice., Drug Enforcement Admin., Off Diversion Control. Available from, as of Jan 7, 2011: https://www.deadiversion.usdoj.gov/drugs_concern/kratom.htm
There is no legitimate medical use for kratom in the US. /Kratom/
DEA; Drugs and Chemicals of Concern. Kratom (Mitragyna speciosa Korth). Dec 2010. US Dept Justice., Drug Enforcement Admin., Off Diversion Control. Available from, as of Jan 7, 2011: https://www.deadiversion.usdoj.gov/drugs_concern/kratom.htm

9 Identification

9.1 Clinical Laboratory Methods

... Ultra trace amount of mitragynine in human urine was ... /determined by high performance liquid chromatography coupled to electrospray tandem mass spectrometry/ (HPLC-ESI/MS/MS). Mitragynine was extracted by methyl t-butyl ether (MTBE) and separated on a HILIC column. The ESI/MS/MS was accomplished using a triple quadrupole mass spectrometer in positive ion detection and multiple reactions monitoring (MRM) mode. Ajmalicine, a mitragynine's structure analog was selected as internal standard (IS) for method development. Quality control (QC) performed at three levels 0.1, 1 and 5 ng/mL of mitragynine in urine gave mean recoveries of 90, 109, and 98% with average relative standard deviation of 22, 12 and 16%, respectively. The regression linearity of mitragynine calibration ranged from 0.01 to 5.0 ng/mL was achieved with correlation coefficient greater than 0.995. A detection limit of 0.02 ng/mL and high precision data within-day and between days analysis were obtained.
Lu S et al; J Chromatog B Analyt Technol Biomed Life Sci 877 (24): 2499-505 (2009)
The aim of this study was to develop a full-scan gas chromatography-mass spectrometry procedure for monitoring kratom or Krypton intake in urine after enzymatic cleavage of conjugates, solid-phase extraction, and trimethylsilylation. With use of reconstructed mass chromatography ... the presence of mitragynine (MG), 16-carboxy-MG, 9-O-demethyl-MG, and/or 9-O-demethyl-16-carboxy-MG could be indicated, and in case of Krypton, ...the additional presence of O-demethyltramadol (ODT) and its nor metabolite could be indicated. ... Depending on the plant type, dose, administration route, and/or sampling time, further metabolites of MG, paynantheine (PAY), speciogynine (SG), and speciociliatine (SC) could be detected. The limits of detection (signal-to-noise ratio of 3) were 100 ng/mL for the parent alkaloids and 50 ng/mL for ODT...
Philipp AA et al; Anal Bioanal Chem. 400(1):127-35 (2011)

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

Precautionary Statement Codes

P261, P264+P265, P272, P280, P302+P352, P305+P351+P338, P321, P333+P317, P337+P317, P362+P364, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary
The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

10.1.2 Hazard Classes and Categories

Skin Sens. 1 (100%)

Eye Irrit. 2 (100%)

10.2 Accidental Release Measures

10.2.1 Disposal Methods

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

11 Toxicity

11.1 Toxicological Information

11.1.1 Interactions

Mitragynine (MG), a major alkaloidal constituent extracted from the plant Mitragyna speciosa Korth, is known to exert an opioid-like activity. ... Previous study showed the involvement of opioid systems in the antinociceptive activity of MG in the tail-pinch and hot-plate tests in mice. In /this/ study, to clarify the opioid receptor subtypes involved in the antinociceptive action of MG, ... the effects of selective antagonists for mu-, delta- and kappa- opioid receptors on antinociception caused by the intracerebroventricular (i.c.v.) injection of MG in the tail-pinch and hot-plate tests in mice /were investigated/. The coadministration of a selective mu-opioid antagonist, cyprodime (1-10 ug, i.c.v.) and the pretreatment with a selective mu1-opioid antagonist naloxonazine (1-3 ug, i.c.v.) significantly antagonized the antinociceptive activities of MG (10 ug, i.c.v.) and morphine (MOR, 3 ug, i.c.v.) in the tail-pinch and hot-plate tests. Naltrindole (1-5 ng, i.c.v.), a selective delta-opioid antagonist, also blocked the effects of MG (10 ug, i.c.v.) without affecting MOR (3 ug, i.c.v.) antinociception. Nor-binaltorphimine, a selective kappa-opioid antagonist, significantly attenuated MG (10 ug, i.c.v.) antinociception in the tail-pinch test but not in the hot-plate test at the dose (1 ug, i.c.v.) that antagonized the antinociceptive effects of the selective kappa-opioid agonist U50,488H in both tests, while it had no effect on MOR antinociception in either tests. These results suggest that antinociception caused by i.c.v. MG is dominantly mediated by mu- and delta-opioid receptor subtypes, and that the selectivity of MG for the supraspinal opioid receptor subtypes differs from that of MOR in mice.
Thongpradichote S et al; Life Sci 62 (16): 1371-8 (1998)

11.1.2 Antidote and Emergency Treatment

... A case of kratom dependence /is described/ in a 44-year-old man with a history of alcohol dependence and anxiety disorder. He demonstrated dependence on kratom with withdrawal symptoms consisting of anxiety, restlessness, tremor, sweating and cravings for the substance. A reducing regime of dihydrocodeine and lofexidine proved effective in treating subjective and objective measures of opioid-like withdrawal phenomena, and withdrawal was relatively short and benign. There are only few reports in the literature of supervised detoxification and drug treatment for kratom dependence. ... Observations /in this case/ support the idea that kratom dependence syndrome is due to short-acting opioid receptor agonist activity, and suggest that dihydrocodeine and lofexidine are effective in supporting detoxification. /Kratom/
McWhirter L, Morris S; Eur Addict Res 16 (4): 229-31 (2010)
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1

11.1.3 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ The primary active alkaloid in kratom is mitragynine; however, other alkaloids are present and account for a variety of effects, which are dose-dependent. Low doses usually produce stimulant effects; higher doses usually produce sedative and euphoric effects. Some users report "lucid dreaming." Individuals who chronically use kratom become thin, their skin darkens (particularly the cheeks), and they experience dry mouth, constipation, and frequent urination. Withdrawal symptoms can include muscle and joint pain, hostility, aggression, eye-watering, and spastic limb movements. /Kratom/
DEA; Selected Intelligence Brief: Herbal Drug Update: Kratom. In: Microgram Bulletin 38 (7): 114 (July 2005)
/SIGNS AND SYMPTOMS/ Users who combine kratom with nervous system depressants may experience respiratory depression, which may cause them to stop breathing. /Kratom/
DEA; Selected Intelligence Brief: Herbal Drug Update: Kratom. In: Microgram Bulletin 38 (7): 114 (July 2005)
/CASE REPORTS/ ... A patient who had abruptly ceased injection hydromorphone abuse self-managed opioid withdrawal and chronic pain using kratom. After co-administering the herb with modafinil he experienced a tonic-clonic seizure, but he reported only modest abstinence once kratom administration stopped. ... The identity of the plant matter he ingested as kratom /was confirmend and no contaminants or adulterants were identified/. ... High-throughput molecular screening and the binding affinity at mu, delta and kappa receptors of mitragynine /were also examined/. ... The predominant alkaloid of kratom, mitragynine, binds mu- and kappa-opioid receptors, but has additional receptor affinities that might augment its effectiveness at mitigating opioid withdrawal...
Boyer EW et al; Addiction 103 (6): 1048-50 (2008)
/CASE REPORTS/ A team of Swedish forensic physicians have concluded that nine young people have died over the past year after having taken the legal drug Krypton. ... /Aside from the leaves and extracts from kratom, Krypton has also been found to contain caffeine and the synthetic opioid O-Desmethyltramadol. O-Desmethyltramadol is a breakdown of the product tramadol, which is prescribed in moderation to alleviate severe pain and when taken as Krypton is turned into tramadol in the liver and becomes more potent. It is due to this high potency contained in the O-Desmethyltramadol that the risk of overdosing is considered high, leading to respiratory paralysis./
Backstrom BG et al; Lakartidningen 107 (50): 3196-7 (2010) (Article in Swedish) .
For more Human Toxicity Excerpts (Complete) data for Mitragynine (8 total), please visit the HSDB record page.

11.1.4 Non-Human Toxicity Excerpts

/BEHAVIORAL STUDIES/ Male Spraque Dawley rats (n=40) with the weight ranging from 250-300 grams, were used in this study. ... Dosages of mitragynine (1.0, 5.0, 10.0 and 30.0 mg/kg) were dissolved in 20% Tween and vehicle was given as control injection. Compounds were administered via intraperitoneal injection 30 to 40 minutes prior to the experiment. The rats were initially accustomed to the experimental room for at least 30 minutes prior to the experiment, following 1 hour observation of locomotor activity in the /open-topped/ box. The rats were placed in the center of the grid and for 1 hour the number of squares entered with all four paws was recorded using a video camera mounted on the ceiling. ... Mitragynine as /the/ major alkaloid from Mitragyna speciosa reduced the locomotor activity of the rats treated with 1.0, 5.0, 10.0 and 30.0 mg/kg as compared with saline as control.
Moklas MAM. et al; Advances in Medical and Dental Sciences (2008)
/ALTERNATIVE and IN VITRO TESTS/ ... The effects of pure alkaloid, mitragynine and a methanolic extract of kratom leaves were investigated on neuromuscular junction and compound nerve action potential. ... Wistar rats were killed by cervical dislocation and decapitated. The phrenic nerve-hemidiaphragms, hemidiaphragms and sciatic nerve were isolated. ... Kratom methanolic extract present at 0.1-1 mg/mL and mitragynine (0.0156 mg/mL) decreased the muscle twitch on the isolated phrenic nerve-hemidiaphragm and hemidiaphragm preparation. Muscle relaxation caused by kratom extract (1 mg/mL) was greater than the effect of mitragynine. Pancuronium and succinylcholine potentiated the effect of kratom extract. It also had a direct relaxation effect on the hemidiaphragm muscle. The muscle relaxation caused by kratom extract was not antagonized by neostigmine, tetraethylammonium and calcium chloride. High concentrations of kratom extract (10-40 mg/mL) and mitragynine (2 mg/mL) blocked the nerve conduction, amplitude and duration of compound nerve action potential. CONCLUSIONS: The mechanism of action of kratom extract might not act as a competitive antagonist of acetylcholine yet its dominant effect was at the neuromuscular junction and not at the skeletal muscle or somatic nerve.
Chittrakarn S et al; J Ethnopharmacol 129 (3): 344-9 (2010)
/ALTERNATIVE and IN VITRO TESTS/ The effect of an indole-alkaloid mitragynine isolated from the Thai medicinal herb kratom (Mitragyna speciosa) on neurogenic contraction of smooth muscle was studied in guinea-pig vas deferens. Mitragynine inhibited the contraction of the vas deferens produced by electrical transmural stimulation. On the other hand, mitragynine failed to affect the responses to norepinephrine and ATP. Mitragynine did not reduce KCl-induced contraction in the presence of tetrodotoxin, prazosin and alpha,beta-methylene ATP. Mitragynine inhibited nicotine- or tyramine-induced contraction. By using the patch-clamp technique, mitragynine was found to block T- and L-type Ca2+ channel currents in N1E-115 neuroblastoma cells. In the Ca2+ measurement by a fluorescent dye method, mitragynine reduced KCl-induced Ca2+ influx in neuroblastoma cells. The ... results suggest that mitragynine inhibits the vas deferens contraction elicited by nerve stimulation, probably through its blockade of neuronal Ca2+ channels.
Matsumoto K et al; Life Sci 78 (2): 187-94 (2005)
/ALTERNATIVE and IN VITRO TESTS/ Effects of mitragynine, an indole alkaloid isolated from Thai medicinal plant kratom (Mitragyna speciosa), on electrically stimulated contraction was studied in the guinea-pig ileum. Mitragynine (1 nM-3 uM) inhibited the ileum contraction elicited by electrical stimulation, and its pD2 value was 6.91 +/- 0.04 (n = 5). Morphine (1 nM-1 uM) also inhibited the electrically stimulated contraction in a concentration-dependent manner (pD2 7.68 +/- 0.11; n = 5). Mitragynine was 10 fold less potent than morphine. Mitragynine (3-10 uM) did not show any effect on the smooth muscle contraction induced by acetylcholine or histamine. Naloxone (10-300 nM) reversed the inhibitory effect of mitragynine on electrically stimulated contraction. Furthermore, naloxone showed a shift of concentration-response curve of mitragynine to the right. There was no significant difference in the affinity of naloxone (i.e. pA2) in the presence of mitragynine or morphine. Mitragynine (3-10 uM) inhibited the naloxone-precipitated withdrawal contraction following a brief (5 min) exposure of the ileum to morphine. Tetrodotoxin (1 uM) and atropine (1 uM) inhibited the withdrawal contraction. The present results suggest that mitragynine inhibits the electrically stimulated contraction of guinea-pig ileum through the opioid receptor.
Watanabe K et al; Life Sci 60 (12): 933-42 (1997)

11.1.5 Populations at Special Risk

One potential user population for kratom is opiate addicts who may attempt to self-treat if they do not have access to methadone programs or if they are reluctant to seek professional treatment. /Kratom/
DEA; Selected Intelligence Brief: Herbal Drug Update: Kratom. In: Microgram Bulletin 38 (7): 115 (July 2005)

11.2 Ecological Information

11.2.1 Ecotoxicity Excerpts

/AQUATIC SPECIES/ The brine shrimp lethality test was used to predict the presence of cytotoxic activity in /Mitragyna speciosa Korth/ extract with some modifications. ... The extracts were tested at 10-100 uL/mL /of artificial sea water/. ... After 24 hours mortality endpoint, the toxicity assessment of three different type of extracts ... was analyzed. The aqueous extract of Mitragyna speciosa Korth showed the lowest toxicity 50 activity against brine shrimp with LC values at 98 uL/mL. The crude alkaloid of the plant exhibited intermediate toxicity activity against brine shrimp larvae with LC values at 62 uL/mL while mitragynine as a major alkaloid exhibited relatively high toxicity to the brine shrimp with LC50 at 44 uL/mL.
Moklas MAM. et al; Advances in Medical and Dental Sciences (2008)

11.2.2 Natural Pollution Sources

Major alkaloid of Mitragyna speciosa Korth., Rubiaceae
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1073

11.2.3 Plant Concentrations

Plants containing mitragynine(1).
Genus species
Mitragyna speciosa KORTH.
Common name
Kratum
Concentration
86 ppm
Plant part
Leaf
(1) USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Mitragynine. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of Jan 11, 2011 https://www.ars-grin.gov/duke/

12 Associated Disorders and Diseases

13 Literature

13.1 Consolidated References

13.2 NLM Curated PubMed Citations

13.3 Springer Nature References

13.4 Thieme References

13.5 Wiley References

13.6 Chemical Co-Occurrences in Literature

13.7 Chemical-Gene Co-Occurrences in Literature

13.8 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 WIPO PATENTSCOPE

14.3 Chemical Co-Occurrences in Patents

14.4 Chemical-Disease Co-Occurrences in Patents

14.5 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Chemical-Target Interactions

16 Biological Test Results

16.1 BioAssay Results

17 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

18 Classification

18.1 MeSH Tree

18.2 ChEBI Ontology

18.3 ChemIDplus

18.4 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

18.5 ChEMBL Target Tree

18.6 UN GHS Classification

18.7 EPA DSSTox Classification

18.8 LOTUS Tree

18.9 MolGenie Organic Chemistry Ontology

19 Information Sources

  1. CAS Common Chemistry
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  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  4. European Chemicals Agency (ECHA)
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    https://echa.europa.eu/web/guest/legal-notice
    (all-S,E)-16,17-Didehydro-9,17-dimethoxy-17,18-seco-20α-yohimban-16-carbonsäuremethylester
    https://echa.europa.eu/substance-information/-/substanceinfo/100.315.156
    (all-S,E)-16,17-Didehydro-9,17-dimethoxy-17,18-seco-20α-yohimban-16-carbonsäuremethylester (EC: 863-118-9)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/309996
  5. FDA Global Substance Registration System (GSRS)
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  6. Hazardous Substances Data Bank (HSDB)
  7. Human Metabolome Database (HMDB)
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    http://www.hmdb.ca/citing
  8. ChEBI
  9. LOTUS - the natural products occurrence database
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    https://lotus.nprod.net/
  10. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  11. Comparative Toxicogenomics Database (CTD)
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    http://ctdbase.org/about/legal.jsp
  12. IUPHAR/BPS Guide to PHARMACOLOGY
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    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  13. Crystallography Open Database (COD)
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    https://creativecommons.org/publicdomain/zero/1.0/
  14. Japan Chemical Substance Dictionary (Nikkaji)
  15. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
  16. Natural Product Activity and Species Source (NPASS)
    2-(3-Ethyl-8-Methoxy-1,2,3,4,6,7,12,12B-Octahydro-Indolo[2,3-A]Quinolizin-2-Yl)-3-Methoxy-Acrylic Acid Methyl Ester
    https://bidd.group/NPASS/compound.php?compoundID=NPC148183
  17. MassBank Europe
  18. MassBank of North America (MoNA)
    LICENSE
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    https://mona.fiehnlab.ucdavis.edu/documentation/license
  19. Metabolomics Workbench
  20. SpectraBase
  21. Springer Nature
  22. Thieme Chemistry
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    https://www.nlm.nih.gov/copyright.html
  28. GHS Classification (UNECE)
  29. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  30. PATENTSCOPE (WIPO)
  31. NCBI
CONTENTS