Running title: Entacapone and Tolcapone inhibit Syn fibrillization * To whom correspondence should be addressed: Prof. Hilal A. Lashuel; Fax: +41 1 693 17 80; Email: [email protected]. Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease (AD). There is considerable consensus that the increased production and/or aggregation of α-synuclein (α...

The catechol-O-methyltransferase (COMT) enzyme metabolises catecholamines. COMT inhibitors are licensed for the adjunctive treatment of Parkinson's disease and are attractive therapeutic candidates for other neuropsychiatric conditions. COMT regulates dopamine levels in the prefrontal cortex (PFC) but plays a lesser role in the striatum. However, its significance in other brain regions is large...

The first effective drugs for Parkinson's disease (PD) were anticholinergics, introduced at the end of 19.th century by Charcot. Since the introduction of levodopa in the sixties of the previous century, many new drugs have emerged for the treatment of Parkinson's disease: dopamine agonists (ergot as well as non-ergot, bromocriptine, pergolide, mirapexine, ropinirole), MAO B inhibitors (selegil...

UDP-glucuronosyltransferase (UGT) is highly expressed in the small intestine and catalyzes the glucuronidation of small molecules, which may affect the oral bioavailability of drugs. However, no method of predicting the in vivo observed fraction of absorbed drug (F(a)F(g)) affected by UGT has yet been established. Here, we investigated the relationship between F(a)F(g) and in vitro clearance of...

Objective(s): Dopamine plays an important role in cognitive functions. Inhibition of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT) may have beneficial effects. Our aim was to assess the effect of COMT inhibitor tolcapone (TCP) on learning and memory in naïve and haloperidol-challenged rats.Materials and Methods: Male ...

Introduction: R-[C]-SKF 82957 is a high-affinity and potent dopamine D1 receptor agonist radioligand, which gives rise to a brainpenetrant lipophilic metabolite. In this study, we demonstrate that systemic administration of catechol-O-methyl transferase (COMT) inhibitors blocks this metabolic pathway, facilitating the use of R-[C]-SKF 82957 to image the high-affinity state of the dopamine D1 re...

BACKGROUND Set-shifting tests represent a reliable paradigm to assess executive functions in humans and animals. In the rat, set-shifting in a cross-maze is a recognized method. In this test, rats must learn an egocentric rule to locate food reinforcement. Once acquired, a second rule, based on visual-cue strategy, allows the location of the food. Ability of rats to shift from the first to the ...