Behavioural, pharmacokinetic, metabolic, and hyperthermic profile of 3,4-Methylenedioxypyrovalerone (MDPV) in the wistar rat

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F18%3A43919390" target="_blank" >RIV/00023752:_____/18:43919390 - isvavai.cz</a>

Result on the web

<a href="https://www.researchgate.net/publication/324724333_Behavioural_Pharmacokinetic_Metabolic_and_Hyperthermic_Profile_of_34-Methylenedioxypyrovalerone_MDPV_in_the_Wistar_Rat" target="_blank" >https://www.researchgate.net/publication/324724333_Behavioural_Pharmacokinetic_Metabolic_and_Hyperthermic_Profile_of_34-Methylenedioxypyrovalerone_MDPV_in_the_Wistar_Rat</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fpsyt.2018.00144" target="_blank" >10.3389/fpsyt.2018.00144</a>

Result language

angličtina

Original language name

Behavioural, pharmacokinetic, metabolic, and hyperthermic profile of 3,4-Methylenedioxypyrovalerone (MDPV) in the wistar rat

Original language description

3,4-methylenedioxypyrovalerone (MDPV) is a potent pyrovalerone cathinone that is substituted for amphetamines by recreational users. We report a comprehensive and detailed description of the effects of subcutaneous MDPV (1–4 mg/kg) on pharmacokinetics, biodistribution and metabolism, acute effects on thermoregulation under isolated and aggregated conditions, locomotion (open field) and sensory gating (prepulse inhibition, PPI). All studies used male Wistar rats. Pharmacokinetics after single dose of 2 mg/kg MDPV was measured over 6 h in serum, brain and lungs. The biotransformation study recorded 24 h urinary levels of MDPV and its metabolites after 4 mg/kg. The effect of 2 mg/kg and 4 mg/kg on body temperature (°C) was measured over 12 h in group- vs. individually-housed rats. In the open field, locomotion (cm) and its spatial distribution were assessed. In PPI, acoustic startle response (ASR), habituation, and PPI were measured (AVG amplitudes). In behavioural experiments, 1, 2, or 4 mg/kg MDPV was administered 15 or 60 min prior to testing. Thermoregulation and behavioural data were analysed using factorial analysis of variance (ANOVA). Peak concentrations of MDPV in sera, lung and brain tissue were reached in under 30 min. While negligible levels of metabolites were detected in tissues, the major metabolites in urine were demethylenyl-MDPV and demethylenyl-methyl-MDPV at levels three-four times higher than the parent drug. We also established a MDPV brain/serum ratio ~2 lasting for ~120 min, consistent with our behavioural observations of locomotor activation and disrupted spatial distribution of behaviour as well as moderate increases in body temperature (exacerbated in group-housed animals). Finally, 4 mg/kg induced stereotypy in the open field and transiently disrupted PPI. Our findings, along with previous research suggest that MDPV is rapidly absorbed, readily crosses the blood-brain barrier and is excreted primarily as metabolites. MDPV acts as a typical stimulant with modest hyperthermic and psychomimetic properties, consistent with a primarily dopaminergic mechanism of action. Since no specific signs of acute toxicity were observed, even at the highest doses used, clinical care and harm-reduction guidance should be in line with that available for other stimulants and cathinones.

Czech name

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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

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/VI20172020056" target="_blank" >VI20172020056: New synthetics drugs - complex interdisciplinary research centre</a><br>

Continuities

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

Publication year

2018

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

9

Issue of the periodical within the volume

Article Number: 144

Country of publishing house

CH - SWITZERLAND

Number of pages

13

Pages from-to

1-13

UT code for WoS article

000430720700001

EID of the result in the Scopus database

2-s2.0-85046661940