Abstract
PurposePyrovalerone derivatives (α-pyrrolidinophenones) form a distinct branch of synthetic cathinones, a popular group of novel psychoactive substances, and exert strong psychostimulatory effects resulting from their high potency to inhibit dopamine (DA) and norepinephrine transporters, with negligible activity at the serotonin (5-HT) transporter. In contrast to the old generation α-pyrrolidinophenones, 3,4-MDPV and α-PVP, there is limited data on the pharmacology and toxicology of the novel analogs. Therefore, the present study assesses the in vivo effects of two new pyrovalerones, PV8 and PV9, along with those of α-PVP, on spontaneous locomotor activities of mice and extracellular DA and 5-HT levels in the mouse striatum.MethodsSpontaneous locomotor activity was measured using Opto-Varimex Auto-Track. Effects of tested compounds on extracellular levels of DA and 5-HT in the striatum were studied by an in vivo microdialysis technique; their concentrations in dialysate fractions were analyzed by high-performance liquid chromatography with electrochemical detection.Resultsα-PVP, PV8 and PV9 stimulated mice locomotor activity (an effect being blocked by D1-dopamine receptor antagonist, SCH 23390), and increased extracellular levels of DA and 5-HT in the striatum. Observed effects depend on dose, time and compound under investigation, with α-PVP being more potent than PV8 and PV9. When used at the same dose, the pyrovalerones produced effects significantly weaker than a model, old generation psychostimulant, methamphetamine.ConclusionsEnhancement of dopaminergic neurotransmission plays a dominant role in the psychomotor stimulation caused by α-PVP, PV8 and PV9. Extending an aliphatic side chain beyond a certain point leads to the decrease in their potency in vivo.
Highlights
Among recreational drug users, there has been a significant increase in the use of novel psychoactive substances (NPS) in recent years
Vertical activities were significantly altered by α-PVP treatment, with a significant effect being observed for dose [F(3, 28) = 6.68; p = 0.0015], interaction [F(33, 308) = 2.106; p = 0.0006], but not time [F(11, 308) = 1.39; p > 0.05]
The psychostimulant effects of all the tested compounds increased with the dose, and no inverted U-shaped dose-effect curve was observed, which is characteristic of many stimulants applied in a wide dosing range [19, 23, 24]; an exception was found for methamphetamine, which induced an increase in vertical activity at a dose of 1 mg/kg, but not at 3 mg/kg
Summary
There has been a significant increase in the use of novel psychoactive substances (NPS) in recent years. Drugs belonging to one of the most prevalent groups of NPS are synthetic cathinones endowed with psychostimulatory action, and synthetic cannabinoids [1]. Synthetic cathinones emerged on the drug market in 2004 and since that time their number has been steadily increasing. In 2015, these drugs constituted one-third of the total NPS seizures in the European Union, Norway and Turkey [1, 2]. Pyrovalerone derivatives (α-pyrrolidinophenones) form a distinct branch of synthetic cathinones. A key feature of the chemical structure of α-pyrrolidinophenones is the replacement of the primary or N-methyl amine with
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
