OBJECTIVE To determine whether the excess mortality observed in patients who received both levodopa and selegiline in a randomised trial could be explained by revised diagnosis of Parkinson's disease, autonomic or cardiovascular effects, more rapid disease progression, or drug interactions. DESIGN Open randomised trial and blind comparison and reclassification of the cause of death of patient...

Monoamine oxidase (MAO) is an enzyme involved in the breakdown of catecholamines including dopamine, norepinephrine, and serotonin. MAO inhibitors were discovered in the late 1950s and were first utilized in the treatment of depression. In 1962 Bernheimer showed that MAO inhibitors could potentiate the antiparkinsonian effect of levodopa but caused severe hypertensive crisis (1). In 1968, Johns...

usually centres on improving dopaminergic func tion in the nigro-striatal pathways. Levo-dopa and selegiline increase the amount of synaptic dopamine available; apomorphine, bromocriptlne and pergolide are agonists at dopamine receptors. Symptoms may also be improved by redressing the balance of dopaminergic and cholinergic activity. Benzhexol, procyclidine and orphenadrine, among others, are a...

Inhibitors of MAO-A and MAO-B are in clinical use for the treatment of psychiatric and neurological disorders respectively. Elucidation of the molecular structure of the active sites of the enzymes has enabled a precise determination of the way in which substrates and inhibitor molecules are metabolized, or inhibit metabolism of substrates, respectively. Despite the knowledge of the strong anti...

Parkinson's disease affects mainly the elderly population and is characterized by tremor, bradykinesia, rigidity and postural abnormalities. As the disease progresses, drug therapy is inevitable and the strategies used aim to correct the imbalance of neurotransmitters in the CNS. Antimuscarinic drugs counteract the excessive effects of acetylcholine while levodopa, dopamine agonists, selegiline...

Monoamine oxidase B (MAO B) is present in the outer mitochondrial membrane occurring in the brain predominantly in glial cells and in serotonergic neurons [Fowler et al., 2005]. It oxidizes amines (for example dopamine) from both endogenous and exogenous sources. MAO B is selectively and irreversibly inhibited by L-deprenyl (selegiline). When the enzyme-substrate complex is formed, the rate-lim...

S t u d y s e l e c t i o n a n d a s s e s s m e n t Studies were selected if they were randomized controlled trials (RCTs) of pharmacologic (dopamine agonists [DAs] plus L-dopa, selegiline plus L-dopa, or catechol O-methyl transferase [COMT] inhibitors plus L-dopa vs L-dopa alone), psychiatric (piracetam or citalopram vs placebo), surgical (pallidotomy, deep brain stimulation [DBS], and fetal...

In this study we synthesized and evaluated a new series of amino and nitro 3-arylcoumarins as hMAO-A and hMAO-B inhibitors. Compounds 2, 3, 5 and 6 presented a better activity and selectivity profile against the hMAO-B isoform (IC50 values between 2 and 6nM) than selegiline. In general, the amino derivatives (4-6) proved to be more selective against MAO-B than the nitro derivatives (1-3). Addit...