Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue-Behavioural, pharmacokinetic and metabolic studies in the Wistar rat

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F16%3A43915004" target="_blank" >RIV/00023752:_____/16:43915004 - isvavai.cz</a>

Alternative codes found

RIV/60461373:22330/16:43901781

Result on the web

<a href="http://www.sciencedirect.com/science/article/pii/S0361923016300983" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0361923016300983</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.brainresbull.2016.05.002" target="_blank" >10.1016/j.brainresbull.2016.05.002</a>

Result language

angličtina

Original language name

Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue-Behavioural, pharmacokinetic and metabolic studies in the Wistar rat

Original language description

Methoxetamine (MXE) is a novel psychoactive compound. We tested, in Wistar rats, the effects of MXE in a series of behavioural tasks, measured its pharmacokinetics and urinary metabolites. Locomotor activity and its spatial characteristics and sensorimotor gating were evaluated after 5, 10 and 40 mg/kg sc. MXE. Pharmacokinetics and brain: serum ratios were evaluated after 10 mg/kg sc. MXE so that peak drug concentration data could be used tocomplement interpretation of maximal behavioural effects. Finally, quantification of metabolites in rat urine collected over 24 h was performed after single bolus of MXE 40 mg/kg sc. 5 and 10 mg/kg MXE induced significant locomotor stimulation, in addition it increased thigmotaxis and decreased time spent in the centre of the open field. By contrast, 40 mg/kg reduced locomotion and increased time spent in the centre of the arena, suggesting sedation/anaesthesia or stereotypy. The duration of effects was present for at least 60-90 min, although for 5 mg/kg, locomotion diminished after 60 min. MXE decreased baseline acoustic startle response and disrupted PPI, irrespective of testing-onset. MXE reduced habituation but only at 60 min. Maximal brain levels of MXE were observed 30 min after administration, remained high at 60 min and progressively declined to around zero after six hours. MXE accumulated in the brain; the brain: serum ratio was 2.06-2.93 throughout the whole observation. The most abundant urinary metabolite was O-desmethylmethoxetamine followed by normethoxetamine. To conclude, MXE acts behaviourally as a typical dissociative anaesthetic with stimulant and anxiogenic effects at lower doses, sedative/anaesthetic effects at higher doses, and as a disruptor of sensorimotor gating. Its duration of action exceeds that of ketamine which is consistent with reports from MXE users. The accumulation of the drug in brain tissue might reflect MXE's stronger potency compared to ketamine and indicate increased toxicity.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FH - Neurology, neuro-surgery, nuero-sciences

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Brain Research Bulletin

ISSN

0361-9230

e-ISSN

—

Volume of the periodical

126

Issue of the periodical within the volume

Part 1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

102-110

UT code for WoS article

000387298400011

EID of the result in the Scopus database

2-s2.0-84975114018