Inviting an author to review:
Find an author and click ‘Invite to review selected article’ near their name.
Search for authorsSearch for similar articles
6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Acute Intoxications Involving α-Pyrrolidinobutiophenone (α-PBP): Results from the Swedish STRIDA Project

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          Many new psychoactive substances (NPS) introduced as recreational drugs have been associated with severe intoxication and death.

          Methods

          Blood and/or urine samples were collected from intoxicated patients treated at Swedish hospitals that participated in the STRIDA project, a nationawide effort to address the growing problem of NPS. In patients undergoing evaluation for drug overdose, α-PBP was identified using liquid chromatography-mass spectrometry. Demographic and clinical data were collected during Poisons Information Centre consultations and retrieved from medical records.

          Results

          From April 2013 to November 2015, 43 patients tested positive for α-PBP. However, α-PBP was never specifically mentioned during consultation but only confirmed analytically. The α-PBP concentrations ranged 2.0–13,200 ng/mL in urine and 2.0–440 ng/mL in serum. The patients were aged 19–57 (mean 34) years, 81% were men, and 73% were known drug addicts. All cases except 1 also involved other NPS and/or classical drugs. MDPV, α-PVP, and other pyrovalerone analogues were the most common other NPS (31 cases; 72%). CNS depressants were detected in 28 cases (65%), with benzodiazepines (16 cases) being most frequent. Main clinical characteristics were agitation/anxiety (59%), tachycardia (54%), and hypertension (37%), and 14 patients (33%) required monitoring in the intensive care unit of which 8 were graded as severe intoxications. No fatalities were reported.

          Conclusion

          Patients with intoxication from α-PBP resembled those by NPS cathinones MDPV and α-PVP. As patients never specifically declared α-PBP intake and poly-drug intoxication was common, they may have been unaware of the actual substance taken.

          Related collections

          Most cited references19

          • Record: found
          • Abstract: found
          • Article: not found

          Pharmacological characterization of designer cathinones in vitro.

          Designer β-keto amphetamines (e.g. cathinones, 'bath salts' and 'research chemicals') have become popular recreational drugs, but their pharmacology is poorly characterized. We determined the potencies of cathinones to inhibit DA, NA and 5-HT transport into transporter-transfected HEK 293 cells, DA and 5-HT efflux from monoamine-preloaded cells, and monoamine receptor binding affinity. Mephedrone, methylone, ethylone, butylone and naphyrone acted as non-selective monoamine uptake inhibitors, similar to cocaine. Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and other entactogens. Cathinone, methcathinone and flephedrone, similar to amphetamine and methamphetamine, acted as preferential DA and NA uptake inhibitors and induced the release of DA. Pyrovalerone and 3,4-methylenedioxypyrovalerone (MDPV) were highly potent and selective DA and NA transporter inhibitors but unlike amphetamines did not evoke the release of monoamines. The non-β-keto amphetamines are trace amine-associated receptor 1 ligands, whereas the cathinones are not. All the cathinones showed high blood-brain barrier permeability in an in vitro model; mephedrone and MDPV exhibited particularly high permeability. Cathinones have considerable pharmacological differences that form the basis of their suggested classification into three groups. The predominant action of all cathinones on the DA transporter is probably associated with a considerable risk of addiction. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products.

            The abuse of psychoactive 'bath salts' containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods. In vitro transporter assays were performed in rat brain synaptosomes and in cells expressing human transporters, while clearance of endogenous dopamine was measured by fast-scan cyclic voltammetry in mouse striatal slices. Assessments of in vivo neurochemistry, locomotor activity, and cardiovascular parameters were carried out in rats. We found that MDPV blocks uptake of [(3)H]dopamine (IC(50)=4.1 nM) and [(3)H]norepinephrine (IC(50)=26 nM) with high potency but has weak effects on uptake of [(3)H]serotonin (IC(50)=3349 nM). In contrast to other psychoactive cathinones (eg, mephedrone), MDPV is not a transporter substrate. The clearance of endogenous dopamine is inhibited by MDPV and cocaine in a similar manner, but MDPV displays greater potency and efficacy. Consistent with in vitro findings, MDPV (0.1-0.3 mg/kg, intravenous) increases extracellular concentrations of dopamine in the nucleus accumbens. Additionally, MDPV (0.1-3.0 mg/kg, subcutaneous) is at least 10 times more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. Our data show that MDPV is a monoamine transporter blocker with increased potency and selectivity for catecholamines when compared with cocaine. The robust stimulation of dopamine transmission by MDPV predicts serious potential for abuse and may provide a mechanism to explain the adverse effects observed in humans taking high doses of 'bath salts' preparations.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Bath salts and synthetic cathinones: an emerging designer drug phenomenon.

              Synthetic cathinones are an emerging class of designer drugs abused for psychostimulant and hallucinogenic effects similar to cocaine, methylenedioxymethamphetamine (MDMA), or other amphetamines. Abuse of synthetic cathinones, frequently included in products sold as 'bath salts', became prevalent in early 2009, leading to legislative classification throughout Europe in 2010 and schedule I classification within the United States in 2011. Recent pre-clinical and clinical studies indicate that dysregulation of central monoamine systems is a principal mechanism of synthetic cathinone action and presumably underlie the behavioral effects and abuse liability associated with these drugs. This review provides insight into the development of synthetic cathinones as substances of abuse, current patterns of their abuse, known mechanisms of their action and toxicology, and the benefits and drawbacks of their classification.
                Bookmark

                Author and article information

                Contributors
                +46-10-4566783 , lisa.franzen@gic.se
                Journal
                J Med Toxicol
                J Med Toxicol
                Journal of Medical Toxicology
                Springer US (New York )
                1556-9039
                1937-6995
                19 June 2018
                19 June 2018
                December 2018
                : 14
                : 4
                : 265-271
                Affiliations
                [1 ]Swedish Poisons Information Centre, SE-171 76 Stockholm, Sweden
                [2 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Laboratory Medicine, , Karolinska Institutet, ; Stockholm, Sweden
                [3 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Department of Clinical Pharmacology, , Karolinska University Laboratory, ; Stockholm, Sweden
                Author information
                http://orcid.org/0000-0002-0648-3838
                Article
                668
                10.1007/s13181-018-0668-2
                6242792
                29923027
                ca2b5684-760a-4512-bdd9-a4a3c7bece9a
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 8 March 2018
                : 18 May 2018
                : 29 May 2018
                Funding
                Funded by: Medical Products Agency
                Categories
                Original Article
                Custom metadata
                © American College of Medical Toxicology 2018

                Toxicology
                α-pbp,new psychoactive substances,nps,cathinone,intoxications
                Toxicology
                α-pbp, new psychoactive substances, nps, cathinone, intoxications

                Comments

                Comment on this article