Unveiling the potential abuse liability of α-D2PV: A novel α-carbon phenyl-substituted synthetic cathinone Article Swipe
Núria Nadal‐Gratacós
,
Sandra Mata
,
Pol Puigseslloses
,
Morgane De Macedo
,
Virginie Lardeux
,
Stéphanie Pain
,
Fuhua Wang
,
Liselott Källsten
,
David Pubill
,
Xavier Berzosa
,
Ján Kehr
,
Marcello Solinas
,
Jordi Camarasa
,
Elena Escubedo
,
Raúl López‐Arnau
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.neuropharm.2025.110425
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.neuropharm.2025.110425
Synthetic cathinones are emerging psychoactive substances designed to mimic the effects of classical psychostimulants. Among them, α-D2PV, a novel pyrrolidine-containing cathinone characterized by a phenyl group on the α-carbon atom, has gained significant attention. This study investigates the in vitro and in silico mechanism of action as well as the abuse liability of α-D2PV using rodent models. Dopamine (DA), noradrenaline (NE), and serotonin (5-HT) uptake inhibition assays were conducted in HEK293 cells expressing the corresponding human monoamine transporter, complemented by molecular docking studies at the DA transporter (DAT). Behavioral studies in male Swiss CD-1 mice assessed locomotor activity and conditioned place preference, while microdialysis and self-administration experiments were performed in male Sprague-Dawley rats. The findings reveal that α-D2PV is a potent DA and NE uptake inhibitor, with minimal activity at the 5-HT transporter (SERT). Docking studies showed that the benzene rings of α-PVP and α-D2PV align precisely in their most stable conformations at DAT. In vivo, α-D2PV elicited dose-dependent hyperlocomotion, thigmotaxis, and rewarding effects in mice, alongside increased extracellular DA levels in the nucleus accumbens of awake rats. Self-administration experiments confirmed α-D2PV's high reinforcing efficacy, indicating a significant risk of abuse in humans. Finally, these results underscore the necessity for continued surveillance of α-D2PV within the illicit drug market. Furthermore, novel synthetic cathinones incorporating a phenyl ring at the α-carbon side chain warrant proactive monitoring due to their potential to retain dopaminergic activity and evade initial legal controls.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.neuropharm.2025.110425
- OA Status
- hybrid
- Cited By
- 2
- References
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- OpenAlex ID
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All OpenAlex metadata
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https://openalex.org/W4408595959Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.neuropharm.2025.110425Digital Object Identifier
- Title
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Unveiling the potential abuse liability of α-D2PV: A novel α-carbon phenyl-substituted synthetic cathinoneWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-03-19Full publication date if available
- Authors
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Núria Nadal‐Gratacós, Sandra Mata, Pol Puigseslloses, Morgane De Macedo, Virginie Lardeux, Stéphanie Pain, Fuhua Wang, Liselott Källsten, David Pubill, Xavier Berzosa, Ján Kehr, Marcello Solinas, Jordi Camarasa, Elena Escubedo, Raúl López‐ArnauList of authors in order
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https://doi.org/10.1016/j.neuropharm.2025.110425Publisher landing page
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hybridOpen access status per OpenAlex
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https://doi.org/10.1016/j.neuropharm.2025.110425Direct OA link when available
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Abuse liability, Cathinone, Liability, Pharmacology, Chemistry, Medicine, Psychology, Business, Neuroscience, Drug, Finance, Dopamine, AmphetamineTop concepts (fields/topics) attached by OpenAlex
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2Total citation count in OpenAlex
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2025: 2Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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