Catechol-O-methyltransferase (COMT, EC 2.1.1.6) plays a central role in the metabolic inactivation of neurotransmitters and neuroactive xenobiotics possessing a catechol motif. 1-(3,4-Dihydroxy-5-nitrophenyl)-2-phenyl-ethanone (BIA 3-202) is a novel nitrocatechol-type inhibitor of COMT, the potential clinical benefit of which is currently being evaluated in the treatment of Parkinson's disease....

5-O-Caffeoylquinic acid (5-CQA) is one of the major bioactive ingredients in some Chinese herbal injections. Occasional anaphylaxis has been reported for these injections during their clinical use, possibly caused by reactive metabolites of 5-CQA. This study aimed at characterizing the bioactivation pathway(s) of 5-CQA and the metabolic enzyme(s) involved. After incubating 5-CQA with GSH and NA...

OBJECTIVE To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does de...

Catechols are a class of substances from natural or synthetic origin that contain a 1,2-dihydroxybenzene group. We have characterized the glucuronidation by rat liver microsomes and by the rat liver recombinant UDP-glucuronosyltransferase isoforms UGT1A6 and UGT2B1 of a series of 42 structurally diverse catechols, including neurotransmitters, polyphenols, drugs, and catechol estrogens. Small ca...

Saviana Di Giovanni, Simona Eleuteri, Katerina E. Paleologou, Guowei Yin, Markus Zweckstetter , Pierre-Alain Carrupt**, and Hilal A. Lashuel From the Laboratory of Molecular Neurobiology and Neuroproteomics, Swiss Federal Institute of Technology Lausanne, SV-BMI-LMNN-AI2351, CH-1015 Lausanne, Switzerland, the Dipartimento di Biologia Evoluzionistica Sperimentale, Università di Bologna Via Selmi...

Background: Evidence-based medicine (EBM) may be used to discard valuable data under the pretext that it does not correspond to the “best” criteria of proof, even when no results complying with these “best” criteria are available. Since their infrequent occurrences make it impossible to assess most adverse effects using randomised clinical trials (RCTs), drug safety offers frequent examples of ...

For the past 30 years levodopa (LD) has been the pharmacological standard of care for treating idiopathic Parkinson’s disease (PD), a neurodegenerative disease of the central nervous system. LD is a pharmacologically inactive precursor, which is converted enzymatically to the neurotransmitter dopamine by a declining population of neurons in the substantia nigra, the most important site of the p...