Pharmacokinetic, ambulatory, and hyperthermic effects of 3,4-methylenedioxy-n-methylcathinone (Methylone) in rats

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F17%3A43919036" target="_blank" >RIV/00023752:_____/17:43919036 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/17:10365440 RIV/00216208:11120/17:43915970 RIV/00216208:11310/17:10365440 RIV/60461373:22330/17:43914339 RIV/00064165:_____/17:10365440

Result on the web

<a href="https://www.frontiersin.org/articles/10.3389/fpsyt.2017.00232/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fpsyt.2017.00232/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fpsyt.2017.00232" target="_blank" >10.3389/fpsyt.2017.00232</a>

Result language

angličtina

Original language name

Pharmacokinetic, ambulatory, and hyperthermic effects of 3,4-methylenedioxy-n-methylcathinone (Methylone) in rats

Original language description

Methylone (3,4-methylenedioxy-N-methylcathinone) is a synthetic cathinone analog of the recreational drug ecstasy. Although it is marketed to recreational users as relatively safe, fatalities due to hyperthermia, serotonin syndrome, and multi-organ system failure have been reported. Since psychopharmacological data remain scarce, we have focused our research on pharmacokinetics, and on a detailed evaluation of temporal effects of methylone and its metabolite nor-methylone on behavior and body temperature in rats. Methylone [5, 10, 20, and 40 mg/kg subcutaneously (s.c.)] and nor-methylone (10 mg/kg s.c.) were used in adolescent male Wistar rats across three behavioral/physiological procedures and in two temporal windows from administration (15 and 60 min) in order to test: locomotor effects in the open field, sensorimotor gating in the test of prepulse inhibition (PPI), and effects on rectal temperature in individually and group-housed rats. Serum and brain pharmacokinetics after 10 mg/kg s.c. over 8 h were analyzed using liquid chromatography mass spectrometry. Serum and brain levels of methylone and nor-methylone peaked at 30 min after administration, both drugs readily penetrated the brain with serum: brain ratio 1:7.97. Methylone dose-dependently increased overall locomotion. It also decrease the amount of time spent in the center of open field arena in dose 20 mg/kg and additionally this dose induced stereotyped circling around the arena walls. The maximum of effects corresponded to the peak of its brain concentrations. Nor-methylone had approximately the same behavioral potency. Methylone also has weak potency to disturb PPI. Behavioral testing was not performed with 40 mg/kg, because it was surprisingly lethal to some animals. Methylone 10 and 20 mg/kg s.c. induced hyperthermic reaction which was more pronounced in group-housed condition relative to individually housed rats. To conclude, methylone increased exploration and/or decreased anxiety in the open field arena and with nor-methylone had short duration of action with effects typical for mixed indirect dopamine–serotonin agonists such as 3,4-metyhlenedioxymethamphetamine (MDMA) or amphetamine. Given the fact that the toxicity was even higher than the known for MDMA and that it can cause hyperthermia it possess a threat to users with the risk for serotonin syndrome especially when used in crowded conditions.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30215 - Psychiatry

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

2017

Confidentiality

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

Name of the periodical

Frontiers in Psychiatry

ISSN

1664-0640

e-ISSN

—

Volume of the periodical

8

Issue of the periodical within the volume

November

Country of publishing house

CH - SWITZERLAND

Number of pages

11

Pages from-to

"Article Number: 232"

UT code for WoS article

000415593900001

EID of the result in the Scopus database

2-s2.0-85034644307