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UWA-101

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UWA-101
Legal status
Legal status
Identifiers
  • 2-(1,3-Benzodioxol-5-yl)-1-cyclopropyl-N-methylethanamine
CAS Number
PubChemCID
ChemSpider
UNII
ChEMBL
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC13H17NO2
Molar mass219.284g·mol−1
3D model (JSmol)
  • C3CC3C(NC)Cc2cc1OCOc1cc2
  • InChI=1S/C13H17NO2/c1-14-11(10-3-4-10)6-9-2-5-12-13(7-9)16-8-15-12/h2,5,7,10-11,14H,3-4,6,8H2,1H3
  • Key:DNROCNZQNQSVOG-UHFFFAOYSA-N

UWA-101(also known asα-cyclopropyl-MDMA) is aphenethylaminederivative researched as a potential treatment forParkinson's disease.Its chemical structure is very similar to that of the illegal drugMDMA,the only difference being the replacement of the α-methylgroup with an α-cyclopropylgroup. MDMA has been found in animal studies and reported in unauthorised human self-experiments to be effective in the short-term relief of side-effects of Parkinson's disease therapy, most notably levodopa-induced dyskinesia.[1][2][3][4]However the illegal status of MDMA and concerns about its potential for recreational use,neurotoxicityand 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 thenoradrenaline transporterand5-HT2Areceptor,while retaining highserotonin transporteraffinity and markedly increasing affinity for thedopamine transporter(and as such, it is one of the few selective SDRIs orserotonin-dopamine reuptake inhibitors). This change causes UWA-101 to lack cytotoxicity and MDMA-like behavioral effects in animals, while retaining similar or slightly improved antidyskinetic effectiveness when compared to MDMA.[6]This research was a continuation of earlier work from the same team led by medicinal chemist Matthew Piggott, at the University of Western Australia, 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 againstBurkitt's lymphomacellsin vitro.[7][8]

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

Another relative isUWA-104( "α-isopropyl-MDMA" ), which is also active.[6]

See also[edit]

References[edit]

  1. ^Schmidt WJ, Mayerhofer A, Meyer A, Kovar KA (September 2002). "Ecstasy counteracts catalepsy in rats, an anti-parkinsonian effect?".Neuroscience Letters.330(3): 251–4.doi:10.1016/s0304-3940(02)00823-6.PMID12270640.S2CID41609012.
  2. ^Iravani MM, Jackson MJ, Kuoppamäki M, Smith LA, Jenner P (October 2003)."3,4-methylenedioxymethamphetamine (ecstasy) inhibits dyskinesia expression and normalizes motor activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates".The Journal of Neuroscience.23(27): 9107–15.doi:10.1523/JNEUROSCI.23-27-09107.2003.PMC6740822.PMID14534244.
  3. ^Lebsanft HB, Kohles T, Kovar KA, Schmidt WJ (March 2005). "3,4-Methylenedioxymethamphetamine counteracts akinesia enantioselectively in rat rotational behavior and catalepsy".Synapse.55(3): 148–55.doi:10.1002/syn.20102.PMID15602749.S2CID24601744.
  4. ^Huot P, Johnston TH, Lewis KD, Koprich JB, Reyes MG, Fox SH, et al. (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".The Journal of Neuroscience.31(19): 7190–8.doi:10.1523/JNEUROSCI.1171-11.2011.PMC6703214.PMID21562283.
  5. ^Jerome I (Spring 2008)."MDMA and Parkinson's: Lots of Research, Few Practical Answers"(PDF).MAPS.XVI(1): 16–18.Archived(PDF)from the original on 2011-09-15.Retrieved2012-04-09.
  6. ^abJohnston TH, Millar Z, Huot P, Wagg K, Thiele S, Salomonczyk D, et al. (May 2012)."A novel MDMA analogue, UWA-101, that lacks psychoactivity and cytotoxicity, enhances L-DOPA benefit in parkinsonian primates".FASEB Journal.26(5): 2154–63.doi:10.1096/fj.11-195016.PMID22345403.S2CID37589231.
  7. ^Gandy MN, McIldowie M, Lewis K, Wasik AM, Salomonczyk D, Wagg K, et al. (2010). "Redesigning the designer drug ecstasy: nonpsychoactive MDMA analogues exhibiting Burkitt's lymphoma cytotoxicity".MedChemComm.1(4): 287–293.doi:10.1039/c0md00108b.
  8. ^Wasik AM, Gandy MN, McIldowie M, Holder MJ, Chamba A, Challa A, et al. (August 2012)."Enhancing the anti-lymphoma potential of 3,4-methylenedioxymethamphetamine ('ecstasy') through iterative chemical redesign: mechanisms and pathways to cell death"(PDF).Investigational New Drugs.30(4): 1471–83.doi:10.1007/s10637-011-9730-5.PMID21850491.S2CID20880580.Archived(PDF)from the original on 2020-03-10.Retrieved2019-09-18.
  9. ^abHuot P, Johnston TH, Lewis KD, Koprich JB, Reyes MG, Fox SH, et al. (July 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.PMID24447715.S2CID37160397.

External links[edit]

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