(Gazi Üniversitesi, Eczacılık Fakültesi, Farmasötik Toksikoloji Anabilim Dalı, Ankara, Türkiye)
İsmet ÇOK
(Gazi Üniversitesi, Eczacılık Fakültesi, Farmasötik Toksikoloji Anabilim Dalı, Ankara, Türkiye)
Yıl: 2020Cilt: 17Sayı: 2ISSN: 1304-530X / 2148-6247Sayfa Aralığı: 235 - 241İngilizce

53 0
Psychoactive Bath Salts and Neurotoxicity Risk
Synthetic cathinones are new designer drugs that possess hallucinogenic and psychostimulant properties, and are designed to mimic the effects of illegal substances such as cocaine, amphetamines, and 3.4-methylenedioxymethamphetamine (ecstasy) and to produce rewarding effects, circumventing existing laws and penalties. Synthetic cathinones, also referred to as ‘bath salts’, have become popular particularly among young people since the mid-2000s. Similar to other psychomotor stimulants, synthetic cathinones have the potential to increase monoamine concentration in the synaptic cleft by targeting the plasma membrane transporters of dopamine, norepinephrine, and serotonin. Because of their structural similarities to amphetamines, it has been suggested that synthetic cathinones may have a neurotoxicity profile similar to that of their amphetamine congeners. Therefore, it has been hypothesized that synthetic cathinones may induce neurotoxicity on monoamine nerve endings in the striatum, hippocampus, and cortex. To date, with regard to synthetic cathinone neurotoxicity, parameters such as monoamine depletion, biosynthetic enzyme inhibition, cytotoxicity, generation of reactive oxygen species, pro-oxidation status, and the ability to induce neuroinflammation were investigated in both in vitro and in vivo experimental studies. Compared with amphetamines, synthetic cathinones appear to have more moderate effects than their amphetamine congeners in terms of neurotoxic effects. However, many synthetic cathinone users take these substances simultaneously with other substances such as benzodiazepines, amphetamines, ecstasy, tetrahydrocannabinol, and ethanol and this abuse can modify their neurotoxic effects. Hence, it is important to understand the underlying mechanism of early neurotoxic effects in case of polysubstance use. In this review, we aimed to present up-to-date information on the abuse potential of synthetic cathinones, their legal status, mechanism of action, and particularly their neurotoxic effects.
DergiDiğerErişime Açık
  • 1. German CL, Fleckenstein AE, Hanson GR. Bath salts and synthetic cathinones: an emerging designer drug phenomenon. Life Sci. 2014;97:2-8.
  • 2. Zawilska JB, Wojcieszak J. Designer cathinones-an emerging class of novel recreational drugs. Forensic Sci Int. 2013;231:42-53.
  • 3. Gershman JA, Fass AD. Synthetic cathinones (‘bath salts’): legal and health care challenges. P T. 2012;37:571-595.
  • 4. Baumann MH, Partilla JS, Lehner KR. Psychoactive “bath salts”: not so soothing. Eur J Pharmacol. 2013;698:1-5.
  • 5. Synthetic Cathinones (Bath Salts): An Emerging Domestic Threat (U.S. Department of Justice National Intelligence Center (July 2011)). Retrieved from pubs44/44571/44571p.pdf
  • 6. Katselou M, Papoutsis I, Nikolaou P, Spiliopoulou C, Athanaselis S. α-PVP (“flakka”): a new synthetic cathinone invades the drug arena. Forensic Toxicology. 2015;34:41-50.
  • 7. Vardakou I, Pistos C, Spiliopoulou C. Drugs for youth via Internet and the example of mephedrone. Toxicol Lett. 2011;20:191-195.
  • 8. World Drug Report 2017: 29.5 million people globally suffer from drug use disorders, opioids the most harmful. (2017). Retrieved from https://
  • 9. Capriola M. Synthetic cathinone abuse. Clin Pharmacol. 2013;5:109-115.
  • 10. Kelly JP. Cathinone derivatives: a review of their chemistry, pharmacology and toxicology. Drug Test Anal. 2011;3:439-453.
  • 11. Coppola M, Mondola R. Synthetic cathinones: chemistry, pharmacology and toxicology of a new class of designer drugs of abuse marketed as “bath salts” or “plant food”. Toxicol Lett. 2012;211:144-149.
  • 12. de Castro A, Lendoiro E, Fernandez-Vega H, Steinmeyer S, LopezRivadulla M, Cruz A. Liquid chromatography tandem mass spectrometry determination of selected synthetic cathinones and two piperazines in oral fluid. Cross reactivity study with an on-site immunoassay device. J Chromatogr A. 2014;1374:93-101.
  • 13. Glennon RA, Dukat M. Synthetic cathinones: a brief overview of overviews with applications to the forensic sciences. Ann Forensic Res Anal. 2017;4. pii: 1040.
  • 14. Corkery JM Guirguis A, Orsolini L, Papanti D, Schifano F. An investigation into the relationship (s) between the different chemical classes of synthetic cathinones and their effects: desired, adverse, toxic. Paper presented at the UNODC Fifth International Conference on Novel Psychoactive Substances. United Nations Office on Drugs and Crime (ONODC) Vienna International Centre, Vienna 23-24 October, 2017.
  • 15. Loeffler G, Hurst D, Penn A, Yung K. Spice, bath salts, and the U.S. military: the emergence of synthetic cannabinoid receptor agonists and cathinones in the U.S. Armed Forces. Mil Med. 2012;177:1041-1048.
  • 16. European Drug Report Trends and Developments (European Monitoring Center for Drugs and Drug Addiction 2017). Retrieved from Lüksemburg: TDAT17001ENN.pdf
  • 17. ‘Zombie’ drug seized in Turkey for the first time. (2017 Oct 15). Hürriyet Daily News. Retrieved from zombie-drug-seized-in-turkey-for-the-first-time-120896
  • 18. Altun B, Çok İ. New pyschoactive substances: synthetic cathinones. J Lit Pharm Sci. 2018;7:136-145.
  • 19. 1-Phenyl-2-(pyrrolidin-1-yl)pentan-1- one (α-PVP) Critical Review Report. (2015 Nov 16-20). Retrieved from Geneva: medicines/access/controlled-substances/5.3_Alpha-PVP_CRev.pdf
  • 20. Banks ML, Worst TJ, Rusyniak DE, Sprague JE. Synthetic cathinones (“bath salts”). J Emerg Med. 2014;46:632-642.
  • 21. Nobrega L, Dinis-Oliveira RJ. The synthetic cathinone alphapyrrolidinovalerophenone (alpha-PVP): pharmacokinetic and pharmacodynamic clinical and forensic aspects. Drug Metab Rev. 2018;50:125-139.
  • 22. Katz DP, Bhattacharya D, Bhattacharya S, Deruiter J, Clark CR, Suppiramaniam V, Dhanasekaran M. Synthetic cathinones: “a khat and mouse game”. Toxicol Lett. 2014;229:349-356.
  • 23. Cozzi NV, Sievert MK, Shulgin AT, Jacob P, 3rd, Ruoho AE. Inhibition of plasma membrane monoamine transporters by beta-ketoamphetamines. Eur J Pharmacol. 1999;381:63-69.
  • 24. Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR. New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol. 2007;47:681-698.
  • 25. Marusich JA, Antonazzo KR, Wiley JL, Blough BE, Partilla JS, Baumann MH. Pharmacology of novel synthetic stimulants structurally related to the “bath salts” constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology. 2014;87:206-213.
  • 26. Weinstein AM, Rosca P, Fattore L, London ED. Synthetic cathinone and cannabinoid designer drugs pose a major risk for public health. Front Psychiatry. 2017;8:156.
  • 27. Angoa-Perez M, Anneken JH, Kuhn DM. Neurotoxicology of synthetic cathinone analogs. Curr Top Behav Neurosci. 2017;32:209-230.
  • 28. Thomas DM, Walker PD, Benjamins JA, Geddes TJ, Kuhn DM. Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation. J Pharmacol Exp Ther. 2004;311:1-7.
  • 29. Anneken JH, Angoa-Perez M, Kuhn DM. 3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: beta-ketoamphetamine modulation of neurotoxicity by the dopamine transporter. J Neurochem. 2015;133:211-222.
  • 30. Hadlock GC, Webb KM, McFadden LM, Chu PW, Ellis JD, Allen SC, Andrenyak DM, Vieira-Brock PL, German CL, Conrad KM, Hoonakker AJ, Gibb JW, Wilkins DG, Hanson GR, Fleckenstein AE. 4-Methylmethcathinone (mephedrone): neuropharmacological effects of a designer stimulant of abuse. J Pharmacol Exp Ther. 2011;339:530- 536.
  • 31. Angoa-Perez M, Kane MJ, Briggs DI, Francescutti DM, Sykes CE, Shah MM, Thomas DM, Kuhn DM. Mephedrone does not damage dopamine nerve endings of the striatum, but enhances the neurotoxicity of methamphetamine, amphetamine, and MDMA. J Neurochem. 2013;125:102-110.
  • 32. den Hollander B, Rozov S, Linden AM, Uusi-Oukari M, Ojanpera I, Korpi ER. Long-term cognitive and neurochemical effects of “bath salt” designer drugs methylone and mephedrone. Pharmacol Biochem Behav. 2013;103:501-509.
  • 33. Lopez-Arnau R, Martinez-Clemente J, Pubill D, Camarasa J, Escubedo E. Evidence of neurotoxicity and cognitive impairment induced by methylone in rats. Basic Clin Pharmacol Toxicol. 2014;115:192-193.
  • 34. Lopez-Arnau R, Martinez-Clemente J, Rodrigo T, Pubill D, Camarasa J, Escubedo E. Neuronal changes and oxidative stress in adolescent rats after repeated exposure to mephedrone. Toxicol Appl Pharmacol. 2015;286:27-35.
  • 35. Ciudad-Roberts A, Duart-Castells L, Camarasa J, Pubill D, Escubedo E. The combination of ethanol with mephedrone increases the signs of neurotoxicity and impairs neurogenesis and learning in adolescent CD-1 mice. Toxicol Appl Pharmacol. 2016;293:10-20.
  • 36. Naseri G, Fazel A, Golalipour MJ, Haghir H, Sadeghian H, Mojarrad M, Hosseini M, Shahrokhi Sabzevar S, Beheshti F, Ghorbani A. Exposure to mephedrone during gestation increases the risk of stillbirth and induces hippocampal neurotoxicity in mice offspring. Neurotoxicol Teratol. 2018;67:10-17.
  • 37. Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8:33-42.
  • 38. Tarkowski P, Jankowski K, Budzyńska B, Biała G, BoguszewskaCzubara A. Potential pro-oxidative effects of single dose of mephedrone in vital organs of mice. Pharmacol Rep. 2018;70:1097-1104.
  • 39. Valente MJ, Bastos ML, Fernandes E, Carvalho F, Guedes de Pinho P, Carvalho M. Neurotoxicity of beta-keto amphetamines: deathly mechanisms elicited by methylone and MDPV in human dopaminergic SH-SY5Y cells. ACS Chem Neurosci. 2017;8:850-859.
  • 40. Lopez-Arnau R, Martinez-Clemente J, Abad S, Pubill D, Camarasa J, Escubedo E. Repeated doses of methylone, a new drug of abuse, induce changes in serotonin and dopamine systems in the mouse. Psychopharmacology (Berl.). 2014;231:3119-3129.
  • 41. Lopez-Arnau R, Martinez-Clemente J, Pubill D, Escubedo E, Camarasa J. Serotonergic impairment and memory deficits in adolescent rats after binge exposure of methylone. J Psychopharmacol. 2014;28:1053- 1063.
  • 42. Rosas-Hernandez H, Cuevas E, Lantz SM, Imam SZ, Rice KC, Gannon BM, Fantegrossi WE, Paule MG, Ali SF. 3,4-Methylenedioxypyrovalerone (MDPV) induces cytotoxic effects on human dopaminergic SH-SY5Y cells. Journal of Drug and Alcohol Research. 2016;5:1-6.
  • 43. Rosas-Hernandez H, Cuevas E, Lantz SM, Rice KC, Gannon BM, Fantegrossi WE, Gonzalez C, Paule MG, Ali SF. Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in bovine brain microvessel endothelial cells. Neurosci Lett. 2016;629:125-130.
  • 44. Angoa-Perez M, Kane MJ, Francescutti DM, Sykes KE, Shah MM, Mohammed AM, Thomas DM, Kuhn DM. Mephedrone, an abused psychoactive component of ‘bath salts’ and methamphetamine congener, does not cause neurotoxicity to dopamine nerve endings of the striatum. J Neurochem. 2012;120:1097-1107.
  • 45. Martinez-Clemente J, Lopez-Arnau R, Abad S, Pubill D, Escubedo E, Camarasa J. Dose and time-dependent selective neurotoxicity induced by mephedrone in mice. PLoS One. 2014;9:e99002.
  • 46. Richman E, Skoller NJ, Fokum B, Burke BA, Hickerson CA, Cotes RO. α-Pyrrolidinopentiophenone (“flakka”) catalyzing catatonia: a case report and literature review. J Addict Med. 2018;12:336-338.
  • 47. Crespi C. Flakka-induced prolonged psychosis. Case Rep Psychiatry. 2016;2016:3460849.
  • 48. Nagai H, Saka K, Nakajima M, Maeda H, Kuroda R, Igarashi A, TsujimuraIto T, Nara A, Komori M, Yoshida K. Sudden death after sustained restraint following self-administration of the designer drug alphapyrrolidinovalerophenone. Int J Cardiol. 2014;172:263-265.
  • 49. Smith DA, Blough BE, Banks ML. Cocaine-like discriminative stimulus effects of amphetamine, cathinone, methamphetamine, and their 3, 4-methylenedioxy analogs in male rhesus monkeys. Psychopharmacology (Berl.). 2017;234:117-127.
  • 50. Giannotti G, Canazza I, Caffino L, Bilel S, Ossato A, Fumagalli F, Marti M. The cathinones MDPV and alpha-PVP elicit different behavioral and molecular effects following acute exposure. Neurotox Res. 2017;32:594- 602.

TÜBİTAK ULAKBİM Ulusal Akademik Ağ ve Bilgi Merkezi Cahit Arf Bilgi Merkezi © 2019 Tüm Hakları Saklıdır.