Neurobiology of Kratom and its main alkaloid mitragynine

Suhaimi, Farah Wahida; Yusoff, Nurul H.M.; Hassan, Rohayanti; Mansor, Sharif Mahsufi; Navaratnam, V.; Müller, Christian P.; Hassan, Zurina

doi:10.1016/j.brainresbull.2016.03.015

Cited by 85 publications

(60 citation statements)

References 104 publications

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“…Mitragynine and 7-hydroxymitragynine are the two alkaloids responsible for the eff ects of kratom and act as full agonists at μ-subtype opioid receptors ( Figure 1). Pharmacological activities are mainly mediated via opioid receptors and neuronal Ca ++ channels with a dominant eff ect at neuromuscular junctions and not in skeletal muscles or somatic nerves (2). In one small trial, pharmacokinetics demonstrated a terminal half-life of about 1 day (3).…”

Section: Discussionmentioning

confidence: 99%

Posterior Reversible Leukoencephalopathy Syndrome After Kratom Ingestion

Castillo¹,

Payne²,

Nugent³

2017

Baylor University Medical Center Proceedings

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Section: Discussionmentioning

confidence: 99%

Posterior Reversible Leukoencephalopathy Syndrome After Kratom Ingestion

Castillo¹,

Payne²,

Nugent³

2017

Baylor University Medical Center Proceedings

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“…In vitro studies have exhibited cytotoxic effects on human neuronal, hepatic, and cardiac myocyte cell lines and have shown neuromuscular blocking effects [21][22][23][24]. Kratom was also reported to inhibit CYP 450 hepatic enzyme, particularly CYP 3A4, 2D6, and 1A2 [29,30]. In toxicological in vivo animal studies, test subjects exhibited adverse effects such as hepatitis, nephrotoxicity, reduced sperm production, addiction and tolerance, long-term cognitive deficits, generalized convulsions, and fatalities with high doses [18,19,[25][26][27][28].…”

Section: Pharmacology and Preclinical Studiesmentioning

confidence: 99%

Kratom from Head to Toe—Case Reviews of Adverse Events and Toxicities

Alsarraf

Myers

Culbreth

et al. 2019

Curr Emerg Hosp Med Rep

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Purpose of Review This review describes case reports for patients with kratom-associated adverse events in order to assist clinicians with patient management. A stepwise approach is proposed for assessing active kratom users as well as considerations for the management of toxicities or withdrawal. Recent Findings Multiple in vitro and in vivo studies illustrate the pharmacologic and toxicologic effects of kratom extract. No randomized controlled trials in humans exist that assess the safety and efficacy of the substance. Cross-sectional surveys from active users and reports from poison control centers have shown acute and chronic physiological and psychological adverse events. Summary Reports of adverse effects associated with kratom use have demonstrated hypothyroidism, hypogonadism, hepatitis, acute respiratory distress syndrome, posterior reversible encephalopathy syndrome, seizure, and coma. Overdose toxidrome leads to respiratory failure, cardiac arrest, and fatalities. Adult and neonatal withdrawal symptoms have also occurred. Clinicians should be aware of the risks and benefits of kratom use.

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“…() and Suhaimi et al . ()]. Most notably, both compounds showed antinociceptive activity, with 7‐OHMG demonstrating higher activity than morphine, tested in tail‐flick and hot‐plate tests in mice after subcutaneous and oral administrations (Matsumoto et al .…”

Section: Introductionmentioning

confidence: 99%

Rate and extent of mitragynine and 7‐hydroxymitragynine blood–brain barrier transport and their intra‐brain distribution: the missing link in pharmacodynamic studies

et al. 2018

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Mitragyna speciosa is reported to be beneficial for the management of chronic pain and opioid withdrawal in the evolving opioid epidemic. Data on the blood-brain barrier (BBB) transport of mitragynine and 7-hydroxymitragynine, the active compounds of the plant, are still lacking and inconclusive. Here, we present for the first time the rate and the extent of mitragynine and 7-hydroxymitragynine transport across the BBB, with an investigation of their post-BBB intra-brain distribution. We utilized an in vitro BBB model to study the rate of BBB permeation of the compounds and their interaction with efflux transporter P-glycoprotein (P-gp). Mitragynine showed higher apical-to-basolateral (A-B, i.e. blood-to-brain side) permeability than 7-hydroxymitragynine. 7-Hydroxymitragynine showed a tendency to efflux, with efflux ratio (B-A/A-B) of 1.39. Both were found to inhibit the P-gp and are also subject to efflux by the P-gp. Assessment of the extent of BBB transport in vivo in rats from unbound brain to plasma concentration ratios (K ) revealed extensive efflux of both compounds, with less than 10 percent of unbound mitragynine and 7-hydroxymitragynine in plasma crossing the BBB. By contrast, the extent of intra-brain distribution was significantly different, with mitragynine having 18-fold higher brain tissue uptake in brain slice assay compared with 7-hydroxymitragynine. Mitragynine showed a moderate capacity to accumulate inside brain parenchymal cells, while 7-hydroxymitragynine showed restricted cellular barrier transport. The presented findings from this systematic investigation of brain pharmacokinetics of mitragynine and 7-hydroxymitragynine are essential for design and interpretation of in vivo experiments aiming to establish exposure-response relationship.

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Neurobiology of Kratom and its main alkaloid mitragynine

Cited by 85 publications

References 104 publications

Posterior Reversible Leukoencephalopathy Syndrome After Kratom Ingestion

Posterior Reversible Leukoencephalopathy Syndrome After Kratom Ingestion

Kratom from Head to Toe—Case Reviews of Adverse Events and Toxicities

Rate and extent of mitragynine and 7‐hydroxymitragynine blood–brain barrier transport and their intra‐brain distribution: the missing link in pharmacodynamic studies

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