The acute effects of methoxphenidine on behaviour and pharmacokinetics profile in animal model

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F25%3A43921488" target="_blank" >RIV/00023752:_____/25:43921488 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10493317 RIV/00216208:11120/25:43928061 RIV/60461373:22330/25:43932000 RIV/60461373:22340/25:43932000 RIV/00064165:_____/25:10493317

Výsledek na webu

<a href="https://doi.org/10.1016/j.pnpbp.2025.111285" target="_blank" >https://doi.org/10.1016/j.pnpbp.2025.111285</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.pnpbp.2025.111285" target="_blank" >10.1016/j.pnpbp.2025.111285</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The acute effects of methoxphenidine on behaviour and pharmacokinetics profile in animal model

Popis výsledku v původním jazyce

Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration: pharmacokinetics in the brain and serum; behaviour (open field and prepulse inhibition), systemic toxicity (lethal dose; LD 50), and histopathology changes in parenchymal organs of Wistar rats. MXP rapidly crossed the blood-brain barrier, reaching peak median concentrations in both serum and brain 30 min post-administration, followed by an elimination phase with a half-life of 2.15 h. Locomotor activity in the open field test displayed a dose-response effect at low to moderate doses (10-20 mg/kg MXP). At higher doses (40 mg/kg), locomotor activity decreased. All doses of MXP significantly disrupted prepulse inhibition and the effect was present during the onset of its action as well as 60 min after treatment. Additionally, MXP demonstrated moderate acute toxicity, with an estimated LD50 of 500 mg/kg when administered subcutaneously. In summary, MXP exhibited a profile similar to typical dissociative anesthetics, producing stimulant and anxiogenic effects at lower doses, sedative effects at higher doses, and disrupting sensorimotor gating. The accumulation of MXP in brain tissue is likely to contribute to acute intoxication in humans, potentially leading to negative experiences. Our findings highlight the potentially dangerous effects of recreational MXP use and underscore the risks of inducing serious adverse health outcomes.

Název v anglickém jazyce

The acute effects of methoxphenidine on behaviour and pharmacokinetics profile in animal model

Popis výsledku anglicky

Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration: pharmacokinetics in the brain and serum; behaviour (open field and prepulse inhibition), systemic toxicity (lethal dose; LD 50), and histopathology changes in parenchymal organs of Wistar rats. MXP rapidly crossed the blood-brain barrier, reaching peak median concentrations in both serum and brain 30 min post-administration, followed by an elimination phase with a half-life of 2.15 h. Locomotor activity in the open field test displayed a dose-response effect at low to moderate doses (10-20 mg/kg MXP). At higher doses (40 mg/kg), locomotor activity decreased. All doses of MXP significantly disrupted prepulse inhibition and the effect was present during the onset of its action as well as 60 min after treatment. Additionally, MXP demonstrated moderate acute toxicity, with an estimated LD50 of 500 mg/kg when administered subcutaneously. In summary, MXP exhibited a profile similar to typical dissociative anesthetics, producing stimulant and anxiogenic effects at lower doses, sedative effects at higher doses, and disrupting sensorimotor gating. The accumulation of MXP in brain tissue is likely to contribute to acute intoxication in humans, potentially leading to negative experiences. Our findings highlight the potentially dangerous effects of recreational MXP use and underscore the risks of inducing serious adverse health outcomes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30215 - Psychiatry

Projekt

<a href="/cs/project/VK01010212" target="_blank" >VK01010212: Nové psychoaktivní substance: forenzně-toxikologické výzkumné centrum</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Progress in Neuro-Psychopharmacology &amp; Biological Psychiatry

ISSN

0278-5846

e-ISSN

1878-4216

Svazek periodika

137

Číslo periodika v rámci svazku

111285

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

1-10

Kód UT WoS článku

001426467800001

EID výsledku v databázi Scopus

2-s2.0-85217152882