UWA-101 (also known as α-cyclopropyl-MDMA) is a phenethylamine derivative invented by Dr Matthew Piggott at the

University of Western Australia The University of Western Australia (UWA) is a public research university in the Australian state of Western Australia. The university's main campus is in Perth, the state capital, with a secondary campus in Albany and various other facilitie ...

, and researched as a potential treatment for

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

. Its chemical structure is very similar to that of the illegal drug

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...

, the only difference being the replacement of the α- methyl group with an α-

cyclopropyl A cyclopropyl group is a chemical structure derived from cyclopropane, and can participate in organic reactions that constitute cycloadditions and rearrangement organic reactions of cyclopropane. The group has an empirical formula of C3H5 and che ...

group. 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. 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. Replacing the α-methyl with a cyclopropyl dramatically reduces affinity for the

noradrenaline transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium- ...

and 5-HT_2A receptor, while retaining high

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...

affinity and markedly increasing affinity for the

dopamine transporter The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dop ...

(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, while retaining similar or slightly improved antidyskinetic effectiveness when compared to MDMA. 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''. UWA-121 is the (''R'')- enantiomer of UWA-101 and the (''S'')-enantiomer is UWA-122. Both are active monoamine reuptake inhibitors. Another relative is UWA-104 ("α-isopropyl-MDMA"), which is also active.

References

External links

Do neurologists dance? A personal experience of Parkinson's disease & MDMA
Tim Lawrence, 2003 {{Phenethylamines Phenethylamines Serotonin–dopamine reuptake inhibitors

See also

References

External links