UWA-101

UWA-101
Legal status
Legal status
Identifiers
CAS Number 1350821-24-7
PubChem (CID) 17756669
ChemSpider 27444374
UNII 0N2Q1RYR1X
ChEMBL CHEMBL3302434
Chemical and physical data
Formula C13H17NO2
Molar mass 219.279 g/mol
3D model (Jmol) Interactive image

UWA-101 (also known as α-cyclopropyl-MDMA) is a phenethylamine derivative invented at the University of Western Australia and researched as a potential treatment for Parkinson's disease. Its chemical structure is very similar to that of the illegal drug MDMA, the only difference being the replacement of the α-methyl group with an α-cyclopropyl group. MDMA has been found in animal studies and reported in unauthorised human self-experiments to be effective in the short-term relief of Parkinson's disease symptoms, especially when used alongside conventional treatment with L-DOPA.[1][2][3][4] However the illegal status of MDMA and concerns about its abuse potential, neurotoxicity and potentially dangerous side effects mean that it is unlikely to be investigated for medical use in this application, and so alternative analogues were investigated.[5]

Replacing the α-methyl with a cyclopropyl dramatically reduces affinity for the noradrenaline transporter and 5-HT2A receptor targets, while retaining high serotonin transporter affinity and markedly increasing affinity for the dopamine transporter (and as such, it is one of the few selective SDRIs or serotonin-dopamine reuptake inhibitors). This change causes UWA-101 to lack cytotoxicity and MDMA-like behavioral effects in animals, but while retaining similar or slightly improved anti-Parkinsonian effectiveness when compared to MDMA.[6] This research was a continuation of earlier work from the same team which showed that replacing the α-methyl group of MDMA with larger aromatic ring systems produced compounds which lacked psychoactivity and neurotoxicity, but had potent anti-cancer effects against Burkitt's lymphoma cells in vitro.[7][8]

UWA-121 is the (R)-enantiomer of UWA-101 and the (S)-enantiomer is UWA-122.[9] Both are active monoamine reuptake inhibitors.[9]

Another relative is UWA-104 ("α-isopropyl-MDMA"), which is also active.[10]

See also

References

  1. ↑ Schmidt WJ, Mayerhofer A, Meyer A, Kovar KA. Ecstasy counteracts catalepsy in rats, an anti-parkinsonian effect? Neuroscience Letters. 2002 Sep 27;330(3):251-4. PMID 12270640
  2. ↑ Iravani MM, Jackson MJ, Kuoppamäki M, Smith LA, Jenner P. 3,4-methylenedioxymethamphetamine (ecstasy) inhibits dyskinesia expression and normalizes motor activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates. Journal of Neuroscience. 2003 Oct 8;23(27):9107-15. PMID 14534244
  3. ↑ Lebsanft HB, Kohles T, Kovar KA, Schmidt WJ. 3,4-Methylenedioxymethamphetamine counteracts akinesia enantioselectively in rat rotational behavior and catalepsy. Synapse. 2005 Mar 1;55(3):148-55. PMID 15602749
  4. ↑ Huot P, Johnston TH, Lewis KD, Koprich JB, Reyes MG, Fox SH, Piggott MJ, Brotchie JM. Characterization of 3,4-methylenedioxymethamphetamine (MDMA) enantiomers in vitro and in the MPTP-lesioned primate: R-MDMA reduces severity of dyskinesia, whereas S-MDMA extends duration of ON-time. Journal of Neuroscience. 2011 May 11;31(19):7190-8. PMID 21562283
  5. ↑ Ilsa Jerome. MDMA and Parkinson’s: Lots of Research, Few Practical Answers. MAPS Vol XVI No 1, pp 16-18, Spring 2008
  6. ↑ Johnston TH, Millar Z, Huot P, Wagg K, Thiele S, Salomonczyk D, Yong-Kee CJ, Gandy MN, McIldowie M, Lewis KD, Gomez-Ramirez J, Lee J, Fox SH, Martin-Iverson M, Nash JE, Piggott MJ, Brotchie JM. A novel MDMA analogue, UWA-101, that lacks psychoactivity and cytotoxicity, enhances l-DOPA benefit in parkinsonian primates. FASEB Journal. 2012 Feb 17. PMID 22345403
  7. ↑ Gandy MN, McIldowie MJ, Lewis K, Wasik AM, Salomonczyk D, Wagg K, Millar ZA, Tindiglia D, Huot P, Johnston TH, Thiele S, Nguyen B, Barnes NM, Brotchie JM, Martin-Iverson MT, Nash JE, Gordon J, Piggott MJ. Redesigning the designer drug ecstasy: nonpsychoactive MDMA analogues exhibiting Burkitt’s lymphoma cytotoxicity. Med. Chem. Comm. 2010; 1: 287–293.
  8. ↑ Wasik AM, Gandy MN, McIldowie M, Holder MJ, Chamba A, Challa A, Lewis KD, Young SP, Scheel-Toellner D, Dyer MJ, Barnes NM, Piggott MJ, Gordon J. Enhancing the anti-lymphoma potential of 3,4-methylenedioxymethamphetamine ('ecstasy') through iterative chemical redesign: mechanisms and pathways to cell death. Investigational New Drugs. 2011 Aug 18. PMID 21850491
  9. 1 2 Huot, Philippe; Johnston, Tom H.; Lewis, Katie D.; Koprich, James B.; Reyes, M. Gabriela; Fox, Susan H.; Piggott, Matthew J.; Brotchie, Jonathan M. (2014). "UWA-121, a mixed dopamine and serotonin re-uptake inhibitor, enhances l-DOPA anti-parkinsonian action without worsening dyskinesia or psychosis-like behaviours in the MPTP-lesioned common marmoset". Neuropharmacology. 82: 76–87. doi:10.1016/j.neuropharm.2014.01.012. ISSN 0028-3908.
  10. ↑ Johnston, T. H.; Millar, Z.; Huot, P.; Wagg, K.; Thiele, S.; Salomonczyk, D.; Yong-Kee, C. J.; Gandy, M. N.; McIldowie, M.; Lewis, K. D.; Gomez-Ramirez, J.; Lee, J.; Fox, S. H.; Martin-Iverson, M.; Nash, J. E.; Piggott, M. J.; Brotchie, J. M. (2012). "A novel MDMA analogue, UWA-101, that lacks psychoactivity and cytotoxicity, enhances L-DOPA benefit in parkinsonian primates". The FASEB Journal. 26 (5): 2154–2163. doi:10.1096/fj.11-195016. ISSN 0892-6638.
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