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      Postmortem distribution of MDPHP in a fatal intoxication case

      case-report

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          Abstract

          The synthetic cathinone (SC) 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP) is structurally correlated to the 3,4-methylenedioxypyrovalerone (MDPV). In recent years, the number of intoxication cases has increased even if little is known about the pharmacokinetics properties. The Postmortem (PM) distribution of MDPHP remains largely unexplored. In these reports, MDPHP levels were quantified in blood, gastric content, and urine. This study aimed to describe the MDPHP PM distribution in several specimens, i.e. central and peripheral blood (CB and PB), right and left vitreous humor (rVH and lVH), gastric content (GCo), urine (U), and hair. The samples were collected from a cocaine-addicted 30-year-old man with a PM interval estimated in 3–4 h. Autopsy examination revealed unspecific findings, i.e. cerebral and pulmonary edema. No injection marks were observed. Toxicological analyses were performed using a multi-analytical approach: headspace gas chromatography for blood alcohol content (BAC), gas chromatography–mass spectrometry (GC–MS) for the main drugs of abuse, liquid chromatography–tandem mass spectrometry (LC–MS–MS) for benzodiazepines, and new psychoactive substances (NPS). BAC was negative (0.02 g/L). MDPHP concentrations were as follows: 1,639.99 ng/mL, CB; 1,601.90 ng/mL, PB; 12,954.13 ng/mL, U; 3,028.54 ng/mL, GCo; 1,846.45 ng/mL, rVH; 2,568.01 ng/mL, lVH; 152.38 (0.0–1.5 cm) and 451.33 (1.5–3.0 cm) ng/mg, hair. Moreover, hair segments were also positive for 3,4-dimethylmethcathinone (DMMC < limit of quantification: 0.01 ng/mg), α-PHP (0.59 ng/mg, 0.0–1.5 cm; 3.07 ng/mg, 1.5–3.0 cm), cocaine (6.58 ng/mg, 0.0–1.5 cm; 22.82 ng/mg, 1.5–3.0 cm), and benzoylecgonine (1.13 ng/mg, 0.0–1.5 cm; 4.30 ng/mg, 1.5–3.0 cm). MDPHP concentrations were significantly higher than those reported in the literature for fatal cases. For these reasons, the cause of death was probably the consumption of a lethal amount of MDPHP. Because CB and PB were similar, PM redistribution was not relevant.

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          Most cited references22

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          Neuropharmacology of Synthetic Cathinones.

          Synthetic cathinones are derivatives of the naturally occurring compound cathinone, the main psychoactive ingredient in the khat plant Catha edulis. Cathinone is the β-keto analog of amphetamine, and all synthetic cathinones display a β-keto moiety in their structure. Several synthetic cathinones are widely prescribed medications (e.g., bupropion, Wellbutrin®), while others are problematic drugs of abuse (e.g., 4-methylmethcathinone, mephedrone). Similar to amphetamines, synthetic cathinones are psychomotor stimulants that exert their effects by impairing the normal function of plasma membrane transporters for dopamine (DAT), norepinephrine (NET), and 5-HT (SERT). Ring-substituted cathinones like mephedrone are transporter substrates that evoke neurotransmitter release by reversing the normal direction of transporter flux (i.e., releasers), whereas pyrrolidine-containing cathinones like 3,4-methylenedioxypyrovalerone (MDPV) are potent transporter inhibitors that block neurotransmitter uptake (i.e., blockers). Regardless of molecular mechanism, all synthetic cathinones increase extracellular monoamine concentrations in the brain, thereby enhancing cell-to-cell monoamine signaling. Here, we briefly review the mechanisms of action, structure-activity relationships, and in vivo pharmacology of synthetic cathinones. Overall, the findings show that certain synthetic cathinones are powerful drugs of abuse that could pose significant risk to users.
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            An updated review on synthetic cathinones

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              • Abstract: found
              • Article: not found

              Structural Modification of the Designer Stimulant α-Pyrrolidinovalerophenone (α-PVP) Influences Potency at Dopamine Transporters

              α -Pyrrolidinovalerophenone ( α -PVP, 7 ) is an illegal synthetic stimulant that is being sold on the clandestine market as “flakka” and “gravel”. The potent pharmacological effects of α -PVP are presumably mediated by inhibition of dopamine uptake at the dopamine transporter (DAT). However, little is known about how structural modification of α -PVP influences activity at DAT. Eleven analogs of α -PVP were synthesized and examined for their ability to inhibit uptake of [ 3 H]dopamine and [ 3 H]serotonin in rat brain synaptosomes. None of the analogs significantly inhibited [ 3 H]serotonin uptake when tested at 10 μ M at the serotonin transporter (SERT). All of the analogs behaved as DAT reuptake inhibitors, but potencies varied over a >1500-fold range. Potency was primarily associated with the nature of the α -substituent, with the more bulky substituents imparting the highest potency. Expansion of the pyrrolidine ring to a piperidine reduced potency up to 10-fold, whereas conformational constraint in the form of an aminotetralone resulted in the least potent compound. Our study provides the first systematic and comparative structure–activity investigation on the ability of α -PVP analogs to act as inhibitors of DAT.

                Author and article information

                Contributors
                Role: Data curation
                Role: Data curationRole: InvestigationRole: Visualization
                Role: InvestigationRole: MethodologyRole: Resources
                Role: Resources
                Role: Visualization
                Role: ResourcesRole: SupervisionRole: Validation
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: ValidationRole: Visualization
                Journal
                J Anal Toxicol
                J Anal Toxicol
                jat
                Journal of Analytical Toxicology
                Oxford University Press (US )
                0146-4760
                1945-2403
                March 2025
                28 November 2024
                28 November 2024
                : 49
                : 2
                : 137-141
                Affiliations
                departmentFT-LAB, Department of Health Science, University of Florence , Florence, 50134, Italy
                departmentFT-LAB, Department of Health Science, University of Florence , Florence, 50134, Italy
                departmentFT-LAB, Department of Health Science, University of Florence , Florence, 50134, Italy
                departmentForensic Pathology Unit, Careggi University Hospital , Florence, 50134, Italy
                departmentDepartment of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence , Florence, 50134, Italy
                departmentDepartment of Medicine and Surgery, Unit of Legal Medicine, University of Parma , Parma 43100, Italy
                departmentDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma , Parma 43121, Italy
                departmentForensic Pathology Unit, Careggi University Hospital , Florence, 50134, Italy
                departmentFT-LAB, Department of Health Science, University of Florence , Florence, 50134, Italy
                Author notes
                *Corresponding author. Forensic Toxicology Laboratory (FT-LAB), Department of Health Science, University of Florence, AOU-CAREGGI, Largo Brambilla, Florence 50134, Italy. E-mail: alexandra.dimitrova@ 123456unifi.it
                [‡]

                co-senior authors.

                Author information
                https://orcid.org/0009-0001-4166-8010
                https://orcid.org/0000-0002-9256-4326
                Article
                bkae092
                10.1093/jat/bkae092
                11982668
                39604091
                79d80f6a-2504-4d82-9c10-40a977bf3d72
                © The Author(s) 2025. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 June 2024
                : 20 November 2024
                : 26 November 2024
                : 25 November 2024
                : 12 December 2024
                Page count
                Pages: 5
                Categories
                Case Report
                AcademicSubjects/MED00305
                AcademicSubjects/SCI01040
                AcademicSubjects/SCI00030

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