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drug ecstasy, is a psychotropic agent whose effects are primarily modulated through the
serotonergic system. In recent years numerous researchers have identified MDMA as
possessing therapeutic activity towards a variety of disease states.Parkinson’s disease (PD) is a common and disabling neurodegenerative disorder. The primary
symptomatic treatment of PD utilises the dopamine precursor levodopa. Long-term levodopa
therapy typically elicits deleterious side-effects, the most significant being levodopa-induced
dyskinesia (LED), the severity of which may negate the therapeutic benefit of levodopa. MDMA
has been demonstrated in primate models to possess both anti-parkinsonian and anti-LED
activity.
Burkitt’s lymphoma (BL) is a malignant disease of the lymphatic system, affecting B-cell
lymphocytes in particular. Recent characterisation of a functioning immunoreactive serotonin
reuptake transporter (SERT) in B-cell lines has been impetus for the investigation of SERT as a
target for drug therapy in BL. MDMA, a known SERT substrate, exhibitss an anti-proliferative
and pro-apoptotic response in a BL cell line (L3055).
This thesis, prompted by recent reports of the therapeutic activity of MDMA in various disease
states, details a medicinal chemistry investigation of MDMA, Chapters One, Two and Three
document the analogues synthesised. These analogues were intended for evaluation as
anti-neoplasties for Burkitt’s lymphoma and for evaluation as therapeutics for the treatment of
PD. This work was conducted in collaboration with Prof. John Gordon and coworkers
(Centre for Immune Regulation at The University of Birmingham), and Dr Jonathan Brotchie
and coworkers (Toronto Western Research Institute).
Additionally a series of putative monoamine oxidase (MAO; EC 1.4.3.4) inhibitors was
conceived, synthesised and assayed (Chapter Four). These compounds were structurally
analogous to selegiline 10, a clinically useful MAO-B inhibitor.
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