Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.

AIMS: d-Deprenyl when used as a positron emission tomography tracer visualizes peripheral inflammation. The major aim of the current study was to identify and investigate the properties of the binding target for d-deprenyl in synovial membrane explants from arthritic patients. MAIN METHODS: Thirty patients diagnosed with arthritis or osteoarthritis were enrolled into the study. Homologous and competitive radioligand binding assays utilizing [3H]d-deprenyl were performed to investigate the biochemical characteristics of the binding site and assess differences in the binding profile in synovial membranes exhibiting varying levels of inflammation. KEY FINDINGS: The [3H]d-deprenyl binding assay confirmed the existence of a single, saturable population of membrane-bound protein binding sites in synovial membrane homogenates. The macroscopically determined level of inflammation correlated with an increase in [3H]d-deprenyl binding affinity, without significant alterations in binding site density. Selective monoamine oxidase B inhibitor, selegiline competed for the same site as [3H]d-deprenyl, but failed to differentiate the samples with regard to their inflammation grade. A monoamine oxidase A inhibitor, pirlindole mesylate showed only weak displacement of [3H]d-deprenyl binding. No significant alterations in monoamine oxidase B expression was detected, thus it was not confirmed whether it could serve as a marker for ongoing inflammation. SIGNIFICANCE: Our study was the first to show the biochemical characteristics of the [3H]d-deprenyl binding site in inflamed human synovium. We confirmed that d-deprenyl could differentiate between patients with varying severity of synovitis in the knee joint by binding to a protein target distinct from monoamine oxidase B.

Orally disintegrating selegiline for the treatment of Parkinson's disease.

The selective monoamine oxidase type B inhibitor selegiline is commonly administered as medical treatment to patients suffering from Parkinson's disease. The clinical value of conventional selegiline is, however, compromised by extensive first-pass metabolism, which reduces its bioavailability and leads to the production of possibly harmful methamfetamine metabolites. This review aims to evaluate a novel, orally disintegrating formulation of selegiline by examining scientific evidence from previous pharmacological and clinical studies. As a result of improved bioavailability, orally disintegrating selegiline can be administered at lower doses than conventional selegiline with similar clinical effect. It also leads to less variable selegiline blood concentrations and produces significantly less methamfetamine metabolites. We conclude that this novel formulation offers an interesting treatment option, especially for patients who report adverse events after initial treatment with conventional selegiline or who suffer from swallowing difficulties.