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Mitragynine

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https://www.readbyqxmd.com/read/29076424/physicochemical-characterization-of-mitragyna-speciosa-alkaloid-extract-and-mitragynine-using-in-vitro-high-throughput-assays
#1
Wai Mun Kong, Zamri Chik, Zahurin Mohamed, Mohammed A Alshawsh
Mitragynine, a major active alkaloid of Mitragyna speciosa, acts as an agonist on μ-opioid receptors, producing effects similar to morphine and other opioids. It has been traditionally utilized to alleviate opiate withdrawal symptoms. Besides consideration about potency and selectivity, a good drug must possess a suitable pharmacokinetic profile, with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-Tox) profile, in order to have a high chance of success in clinical trials. The purity of mitragynine in a Mitragyna speciosa alkaloid extract (MSAE) was determined using Ultra-Fast Liquid Chromatography (UFLC)...
October 26, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28966251/enhancement-of-endothelial-barrier-permeability-by-mitragynine
#2
Toshiyuki Matsunaga, Yoshifumi Morikawa, Kyoko Kamase, Misato Horinouchi, Yasuhide Sasajima, Koichi Suenami, Kiyohito Sato, Yuji Takekoshi, Satoshi Endo, Ossama El-Kabbani, Akira Ikari
Persistent inhalation of mitragynine (MG), a major alkaloid in the leaves of Mitragyna speciosa, causes various systemic adverse effects such as seizure, diarrhea and arthralgias, but its toxicity to endothelial cells and effects on barrier function of the cells are poorly understood. In this study, we compared toxicities of MG and mitraphylline, another constituent of the leaves, against human aortic endothelial (HAE), bronchial BEAS-2B, neuronal SK-N-SH, hepatic HepG2, kidney HEK293, gastric MKN45, colon DLD1, lung A549, breast MCF7 and prostate LNCaP cells, and found that MG, but not mitraphylline, shows higher toxicity to HAE cells compared to the other cells...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28950813/a-review-on-the-antinociceptive-effects-of-mitragyna-speciosa-and-its-derivatives-in-animal-model
#3
Kok-Yong Chin, Wun Fui Mark-Lee
Mitragyna speciosa is a tropical plant with narcotic effects. The antinociceptive effects of its crude extracts, bioactive compounds and structurally modified derivatives have been examined in rodent models. This review aims to summarize the evidence on the antinociceptive effects of M. speciosa and its derivatives and explore whether they can offer an alternative to morphine in pain management. Methanolic and alkaloid extracts of M. speciosa were shown to attenuate the nociceptive response in rodents. Mitragynine and 7-hydroxymitragynine offered better antinociceptive effects than crude extracts...
September 25, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28868040/novel-psychoactive-substances-recent-progress-on-neuropharmacological-mechanisms-of-action-for-selected-drugs
#4
REVIEW
Zurina Hassan, Oliver G Bosch, Darshan Singh, Suresh Narayanan, B Vicknasingam Kasinather, Erich Seifritz, Johannes Kornhuber, Boris B Quednow, Christian P Müller
A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28830758/the-medicinal-chemistry-and-neuropharmacology-of-kratom-a-preliminary-discussion-of-a-promising-medicinal-plant-and-analysis-of-its-potential-for-abuse
#5
REVIEW
Andrew C Kruegel, Oliver Grundmann
The leaves of Mitragyna speciosa (commonly known as kratom), a tree endogenous to parts of Southeast Asia, have been used traditionally for their stimulant, mood-elevating, and analgesic effects and have recently attracted significant attention due to increased use in Western cultures as an alternative medicine. The plant's active alkaloid constituents, mitragynine and 7-hydroxymitragynine, have been shown to modulate opioid receptors, acting as partial agonists at mu-opioid receptors and competitive antagonists at kappa- and delta-opioid receptors...
August 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28830118/two-fatal-intoxications-involving-3-methoxyphencyclidine
#6
Christie Mitchell-Mata, Brittany Thomas, Brianna Peterson, Fiona Couper
3- and 4-methoxyphencyclidine (3-MeO-PCP, 4-MeO-PCP), structural analogs of phencyclidine (PCP), were among the first legal PCP alternatives to show up on the novel psychoactive substances (NPS) market in Europe in the 2000s. Their structural similarities to PCP and ketamine likely contribute to their demonstrated dissociative anesthetic effects. Limited information exists in the literature about toxic and lethal concentrations of these drugs in biological samples. This case report presents the first two death cases in Washington State in which 3-MeO-PCP was identified...
July 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28687506/effects-of-alkaloid-rich-extract-from-mitragyna-speciosa-korth-havil-on-naloxone-precipitated-morphine-withdrawal-symptoms-and-local-field-potential-in-the-nucleus-accumbens-of-mice
#7
Dania Cheaha, Chayaporn Reakkamnuan, Jakkrit Nukitram, Somsmorn Chittrakarn, Pimpimol Phukpattaranont, Niwat Keawpradub, Ekkasit Kumarnsit
ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) Havil. (M. speciosa) is among the most well-known plants used in ethnic practice of Southeast Asia. It has gained increasing attention as a plant with potential to substitute morphine in addiction treatment program. However, its action on the central nervous system is controversial. AIM OF THE STUDY: This study investigated the effects of M. speciosa alkaloid extract on naloxone-precipitated morphine withdrawal and neural signaling in the nucleus accumbens (NAc, brain reward center) of mice...
July 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28676005/opioids-in-the-frame-of-new-psychoactive-substances-network-a-complex-pharmacological-and-toxicological-issue
#8
Ludovic Ventura, Félix Carvalho, Ricardo Jorge Dinis-Oliveira
New psychoactive substances (NPS), often referred to as "legal highs" or "designer drugs", are derivatives and analogues of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. Due to inefficient monitoring techniques, as well as limited knowledge concerning long-time effects of NPS, further studies regarding such compounds are constantly required. This systematic review aims to gather the state of the art regarding chemical, molecular pharmacology and toxicological information of opioid class of NPS...
July 4, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28559179/opioid-receptors-mediate-the-acquisition-but-not-the-expression-of-mitragynine-induced-conditioned-place-preference-in-rats
#9
Nurul H M Yusoff, Sharif M Mansor, Christian P Müller, Zurina Hassan
Mitragynine is the main psychoactive ingredient of the herbal drug preparation Kratom (Ketum), derived from the plant Mitragyna speciosa. Kratom is a widely abused drug in Southeast Asian and has a psychostimulant profile at low-medium doses, while high doses have opioidergic effects. Mitragynine was shown to possess opiate receptor affinity. However, its role in the behavioural effects of mitragynine is unclear. Here we asked whether the reinforcing effects of mitragynine are mediated by opiate receptors using a conditioned place preference (CPP) paradigm in rats...
August 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28551311/evaluation-of-pharmacokinetics-and-blood-brain-barrier-permeability-of-mitragynine-using-in-vivo-microdialysis-technique
#10
Wai Mun Kong, Zahurin Mohamed, Mohammed A Alshawsh, Zamri Chik
A microdialysis system coupled with a sensitive ultra-fast liquid chromatography-mass spectrometry (UFLC-MS) method was developed for the pharmacokinetic analysis of mitragynine in rat blood and striatum. Mitragynine is an active alkaloid of Mitragyna speciosa and has been proposed to be used for opioid withdrawal therapy. In this study, chromatographic separation was performed in a gradient elution mode with 0.1% formic acid and acetonitrile on a Zorbax Eclipse C18 column. The mass spectrometric (MS) analysis was carried out in a positive electrospray mode and mitragynine ion (m/z 399...
September 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28443503/kratom-and-future-treatment-for-the-opioids-addiction-and-chronic-pain-periculo-beneficium
#11
Ismaliza Ismail, Suzaily Wahab, Hatta Sidi, Srijit Das, Loo Jiann Lin, Rosdinom Razali
Kratom (Mitragynaspeciosa), a natural existing plant found in South-East Asia, is tradi-tionally used as an herb to help to elevate a person's energy and also to treat numerous medical ailments. Other than the analgesic property, kratom has been used as an agent to overcome opioid withdrawal as it contains natural alkaloids, i.e. mitragynine, 7-hydroxymitragynine, and MGM-9, which has agonist affinity on the opioid receptors, including mu (μ) and kappa (κ). The role of neural reward pathway linked to μ-opioid receptors and both dopaminergic and GABA-ergic interneurons that express μ-opioid receptors were deliberated...
April 25, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28293192/indole-alkaloids-from-plants-as-potential-leads-for-antidepressant-drugs-a-mini-review
#12
Hazrulrizawati A Hamid, Aizi N M Ramli, Mashitah M Yusoff
Depression is the most common illness observed in the elderly, adults, and children. Antidepressants prescribed are usually synthetic drugs and these can sometimes cause a wide range of unpleasant side effects. Current research is focussed on natural products from plants as they are a rich source of potent new drug leads. Besides Hypericum perforatum (St. John's wort), the plants studied include Passiflora incarnata L. (passion flower), Mitragyna speciosa (kratom), Piper methysticum G. Forst (kava) and Valeriana officinalis L...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28089300/mitragynine-concentrations-in-two-fatalities
#13
Olwen Domingo, Gabriele Roider, Andreas Stöver, Matthias Graw, Frank Musshoff, Hans Sachs, Wolfgang Bicker
Two cases of fatalities are reported of which the recreational use of Mitragyna speciosa ("kratom") could be confirmed. One of these cases presents with one of the highest postmortem mitragynine concentrations published to date. Our results show that even extremely high mitragynine blood concentrations following the consumption of kratom do not necessarily have to be the direct cause of death in such fatalities as a result of an acute overdose. The two cases are compared with regard to the differences in mitragynine concentrations detected and the role of mitragynine in the death of the subjects...
February 2017: Forensic Science International
https://www.readbyqxmd.com/read/28072812/is-kratom-the-new-legal-high-on-the-block-the-case-of-an-emerging-opioid-receptor-agonist-with-substance-abuse-potential
#14
George C Chang-Chien, Charles A Odonkor, Prin Amorapanth
Kratom is an unscheduled opioid receptor agonist that comes in the form of dietary supplements currently being abused by chronic pain patients on prescription opioids. Active alkaloids isolated from kratom such as mitragynine and 7-hydroxymitragynine are thought to act on mu- and delta-opioid receptors as well as alpha-2 adrenergic and 5-HT2A receptors. Animal studies suggest that kratom may be more potent than morphine. Consequently, kratom consumption produces analgesic and euphoric feelings among users. In particular, some chronic pain patients on opioids take kratom to counteract the effects of opioid withdrawal...
January 2017: Pain Physician
https://www.readbyqxmd.com/read/27951469/-evaluation-of-ion-mobility-spectrometry-for-the-detection-of-mitragynine-in-kratom-products
#15
Nathan Fuenffinger, Melissa Ritchie, Ashley Ruth, Connie Gryniewicz-Ruzicka
An ion mobility spectrometry (IMS) method was developed for the rapid detection of mitragynine, the most abundant alkaloid in Mitragyna speciosa also known as kratom. The peak corresponding to the mitragynine protonated ion exhibited a reduced ion mobility of 0.95±0.00014cm(2)/(Vs), and the mitragynine limit of detection using IMS was 0.5ng. The IMS method was applied to the analysis of 15 commercial samples suspected of containing kratom. IMS results were compared to those obtained from liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of the same samples...
February 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27893147/update-on-the-pharmacology-and-legal-status-of-kratom
#16
Walter C Prozialeck
Kratom (Mitragyna speciosa) is a plant indigenous to Southeast Asia. Its leaves and the teas brewed from them have long been used by people in that region to stave off fatigue and to manage pain and opioid withdrawal. In a comprehensive review published in 2012, Prozialeck et al presented evidence that kratom had been increasingly used for the self-management of opioid withdrawal and pain in the United States. At the time, kratom was classified as a legal herbal product by the US Drug Enforcement Administration...
December 1, 2016: Journal of the American Osteopathic Association
https://www.readbyqxmd.com/read/27752985/suspected-adulteration-of-commercial-kratom-products-with-7-hydroxymitragynine
#17
Alicia G Lydecker, Abhisheak Sharma, Christopher R McCurdy, Bonnie A Avery, Kavita M Babu, Edward W Boyer
INTRODUCTION: Kratom (Mitragyna speciosa), a plant native to Southeast Asia, has been used for centuries for its stimulant and opium-like effects. Mitragynine and 7-hydroxymitragynine, exclusive to M. speciosa, are the alkaloids primary responsible for Kratom's biologic and psychoactive profile, and likely contribute to its problematic use. We purchased several commercially available Kratom analogs for analysis and through our results, present evidence of probable adulteration with the highly potent and addictive plant alkaloid, 7-hydroxymitragynine...
December 2016: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/27725074/determination-of-mitragynine-in-mitragyna-speciosa-raw-materials-and-finished-products-by-liquid-chromatography-with-uv-detection-single-laboratory-validation
#18
Elizabeth M Mudge, Paula N Brown
Mitragyna speciosa (kratom) is a tree indigenous to Southeast Asia, and its leaves are used in herbal formulations because they contain indole alkaloids mitragynine and 7-hydroxy (7-OH) mitragynine. An HPLC method was developed, optimized, and validated using single-laboratory validation guidelines to quantify mitragynine in kratom raw materials and finished products. The method optimization evaluated several extraction parameters including solvent type, solvent volume, time, and extraction method. The separation of the mitragynine alkaloids was achieved in 18 min with a fused-core C18 EVO column using gradient separation with ammonium bicarbonate (pH 9...
October 8, 2016: Journal of AOAC International
https://www.readbyqxmd.com/read/27669103/do-you-get-what-you-paid-for-an-examination-of-products-advertised-as-kratom
#19
O Hayden Griffin, Jace A Daniels, Elizabeth A Gardner
Although some novel psychoactive substances (NPS) are newly discovered chemicals, others are traditional or indigenous substances that are introduced to new markets. One of these latter substances is a plant many people refer to as kratom. Indigenous to Southeast Asia and used for a variety of instrumental and recreational purposes, kratom has recently become available to Western drug users. Kratom is somewhat unique in that the plant contains two different psychoactive chemicals, which have both stimulant (mitragynine) and narcotic (7-hydroxymitragynine) properties...
November 2016: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/27556704/mitragynine-corynantheidine-pseudoindoxyls-as-opioid-analgesics-with-mu-agonism-and-delta-antagonism-which-do-not-recruit-%C3%AE-arrestin-2
#20
András Váradi, Gina F Marrone, Travis C Palmer, Ankita Narayan, Márton R Szabó, Valerie Le Rouzic, Steven G Grinnell, Joan J Subrath, Evelyn Warner, Sanjay Kalra, Amanda Hunkele, Jeremy Pagirsky, Shainnel O Eans, Jessica M Medina, Jin Xu, Ying-Xian Pan, Attila Borics, Gavril W Pasternak, Jay P McLaughlin, Susruta Majumdar
Natural products found in Mitragyna speciosa, commonly known as kratom, represent diverse scaffolds (indole, indolenine, and spiro pseudoindoxyl) with opioid activity, providing opportunities to better understand opioid pharmacology. Herein, we report the pharmacology and SAR studies both in vitro and in vivo of mitragynine pseudoindoxyl (3), an oxidative rearrangement product of the corynanthe alkaloid mitragynine. 3 and its corresponding corynantheidine analogs show promise as potent analgesics with a mechanism of action that includes mu opioid receptor agonism/delta opioid receptor antagonism...
September 22, 2016: Journal of Medicinal Chemistry
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