UWA-101

UWA-101
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C13H17NO2
Molar mass 219.279 g/mol
3D model (JSmol)

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 potential for recreational use, 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 (Sep 2002). "Ecstasy counteracts catalepsy in rats, an anti-parkinsonian effect?". Neuroscience Letters. 330 (3): 251–4. PMID 12270640. doi:10.1016/s0304-3940(02)00823-6.
  2. ↑ Iravani, MM; Jackson, MJ; Kuoppamäki, M; Smith, LA; Jenner, P (Oct 2003). "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. 23 (27): 9107–15. PMID 14534244.
  3. ↑ Lebsanft, HB; Kohles, T; Kovar, KA; Schmidt, WJ (Mar 2005). "3,4-Methylenedioxymethamphetamine counteracts akinesia enantioselectively in rat rotational behavior and catalepsy". Synapse. 55 (3): 148–55. PMID 15602749. doi:10.1002/syn.20102.
  4. ↑ Huot, P; Johnston, TH; Lewis, KD; Koprich, JB; Reyes, MG; Fox, SH; Piggott, MJ; Brotchie, JM (May 2011). "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. 31 (19): 7190–8. PMID 21562283. doi:10.1523/JNEUROSCI.1171-11.2011.
  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 (2012). "A novel MDMA analogue, UWA-101, that lacks psychoactivity and cytotoxicity, enhances l-DOPA benefit in parkinsonian primates". FASEB Journal. 26: 2154–63. PMID 22345403. doi:10.1096/fj.11-195016.
  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 (2010). "Redesigning the designer drug ecstasy: nonpsychoactive MDMA analogues exhibiting Burkitt's lymphoma cytotoxicity". Med. Chem. Comm. 1: 287–293. doi:10.1039/c0md00108b.
  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 (2011). "Enhancing the anti-lymphoma potential of 3,4-methylenedioxymethamphetamine ('ecstasy') through iterative chemical redesign: mechanisms and pathways to cell death". Investigational New Drugs. 30: 1471–83. PMID 21850491. doi:10.1007/s10637-011-9730-5.
  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. ISSN 0028-3908. PMID 24447715. doi:10.1016/j.neuropharm.2014.01.012.
  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. ISSN 0892-6638. PMID 22345403. doi:10.1096/fj.11-195016.
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