(-)-Mitragynine

627.6

398.50

200-659-6

White amorphous powder

29339900

221.48000

3.88

1.2±0.1 g/cm3

104 °C

235 °C

9℃

1.605

Soluble in alcohol, chloroform, acetic acid

-20°C Freezer

D +39° (chloroform)

UN1230 - class 3 - PG 2 - Methanol, solution

1

11-23/24/25-39/23/24/25-36/37/38-22

7-16-36/37-45-26

F,T

P210-P260-P280-P301 + P310-P311

H225-H301 + H311 + H331-H370

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.

|Warning|H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P264, P272, P280, P302+P352, P305+P351+P338, P321, P333+P313, P337+P313, P363, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

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.

/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.

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/

Major alkaloid of Mitragyna speciosa Korth., Rubiaceae

... 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.

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.|... 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.|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.

... Mitragynine (MIT), a mu-opioid agonist with antinociceptive and antitussive properties...|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.

... 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/|/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/|/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/|/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/

/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/|/SIGNS AND SYMPTOMS/ Users who combine kratom with nervous system depressants may experience respiratory depression, which may cause them to stop breathing. /Kratom/|/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...|/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./|For more Human Toxicity Excerpts (Complete) data for Mitragynine (8 total), please visit the HSDB record page.

Kratom

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.|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.|... 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/|There is no legitimate medical use for kratom in the US. /Kratom/

... 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.|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...