Basic Aspects of Catechol-O-Methyltransferase and the Clinical Applications of its Inhibitors

Volume 95 of International Review of Neurobiology focuses on Catechol-O-methyltransferase inhibition, and its clinical application in relation to Parkinson’s disease. Chapters cover COMT gene and proteins, L-dopa treatment in Parkinson’s disease, the latest research on COMT inhibitors and their clinical applications, as well as future prospects for their use.

Up-to-date summary of biochemistry and pharmacology of COMT and its inhibitorsPreclinical models in COMT inhibitor devlopmentTransgenic COMT mice – latest information summarizedChemistry of COMT inhibitors and their design with molecular modellingCOMT gene and its regulation and relation to dopamine related diseasesRole of cofactor SAM regulation in relation to homocysteineNonclinical and clinical safety of COMT inhibitors summarizedFuture prospects of COMT inhibitors in Parkinson’s disease

1. Introductory remarks: Catechol-O-methyltransferase inhibition: an innovative approach to enhance L-dopa therapy in Parkinson’s disease with dual enzyme inhibition

Erkki Nissinen

2. The catechol-O-methyltransferase gene, its regulation and polymorphisms

Elizabeth M. Tunbridge

3. Distribution and functions of catechol-O-methyltransferase proteins: do recent findings change the picture?

Timo T. Myöhänen & Pekka T. Männistö

4. Catechol-O-methyltransferase enzyme: Cofactor S-adenosyl-L-methionine and related mechanisms

Thomas Müller

5. Biochemistry and pharmacology of catechol-O-methyltrasferase inhibitors

Erkki Nissinen and Pekka T. Männistö

6. The Chemistry of Catechol-O-methyltransferase Inhibitors

David A. Learmonth, László E. Kiss and Patrício Soares-da-Silva

7. Toxicology and safety of COMT inhibitors

Kristiina Haasio

8. Catechol-O-methyltransferase inhibitors in preclinical models as adjuncts of the L-dopa treatment

Concepció Marin, J.A. Obeso

9. Problems with the present inhibitors and a relevance of new and improved COMT inhibitors in Parkinson’s disease

Seppo Kaakkola

10. Catechol-O-methyltransferase and pain

Oleg Kambur & Pekka T. Männistö