Cyclic-Nucleotide Phosphodiesterases in the Central Nervous System

This book reviews advances in understanding phosphodiesteraseswithin the central nervous system and their therapeuticapplications. A range of expert authors from both academia andindustry describe these, then focus on the areas of greatestscientific and medical interest to provide more detailed coverage.Therapeutic and drug discovery applications are covered fordiseases including Alzheimer's, Parkinson's, schizophrenia,erectile dysfunction, and spinal cord injuries. There is also achapter on drug discovery tools such as in vitro assays and X-raystructures for medicinal chemistry studies.

PREFACE viiCONTRIBUTORS ix1 PHOSPHODIESTERASES AND CYCLIC NUCLEOTIDE SIGNALING IN THECNS 1Marco Conti and Wito Richter2 PUTTING TOGETHER THE PIECES OF PHOSPHODIESTERASEDISTRIBUTION PATTERNS IN THE BRAIN: A JIGSAW PUZZLE OF CYCLICNUCLEOTIDE REGULATION 47Michy P. Kelly3 COMPARTMENTALIZATION AND REGULATION OF CYCLIC NUCLEOTIDESIGNALING IN THE CNS 59Manuela Zaccolo and Alessandra Stangherlin4 PHARMACOLOGICAL MANIPULATION OF CYCLIC NUCLEOTIDEPHOSPHODIESTERASE SIGNALING FOR THE TREATMENT OF NEUROLOGICAL ANDPSYCHIATRIC DISORDERS IN THE BRAIN 77Frank S. Menniti, Niels Plath, Niels Svenstrup, and ChristopherJ. Schmidt5 RECENT RESULTS IN PHOSPHODIESTERASE INHIBITOR DEVELOPMENTAND CNS APPLICATIONS 115David P. Rotella6 CRYSTAL STRUCTURES OF PHOSPHODIESTERASES AND IMPLICATION ONDISCOVERY OF INHIBITORS 145Hengming Ke, Huanchen Wang, Mengchun Ye, and YingchunHuang7 INHIBITION OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASES TOREGULATE MEMORY 171Han-Ting Zhang, Ying Xu, and James O'Donnell8 EMERGING ROLE FOR PDE4 IN NEUROPSYCHIATRIC DISORDERS:TRANSLATING ADVANCES FROM GENETIC STUDIES INTO RELEVANT THERAPEUTICSTRATEGIES 211Sandra P. Zoubovsky, Nicholas J. Brandon, and Akira Sawa9 BEYOND ERECTILE DYSFUNCTION: UNDERSTANDING PDE5 ACTIVITY INTHE CENTRAL NERVOUS SYSTEM 223Eva P.P. Bollen, Kris Rutten, Olga A.H. Reneerkens, Harry M.W.Steinbusch, and Jos Prickaerts10 MOLECULAR AND CELLULAR UNDERSTANDING OF PDE10A: ADUAL-SUBSTRATE PHOSPHODIESTERASE WITH THERAPEUTIC POTENTIAL TOMODULATE BASAL GANGLIA FUNCTION 247Erik I. Charych and Nicholas J. Brandon11 ROLE OF CYCLIC NUCLEOTIDE SIGNALING AND PHOSPHODIESTERASEACTIVATION IN THEMODULATION OF ELECTROPHYSIOLOGICAL ACTIVITY OF CENTRAL NEURONS269Sarah Threlfell and Anthony R. West12 THE ROLE OF PHOSPHODIESTERASES IN DOPAMINE SYSTEMSGOVERNING MOTIVATED BEHAVIOR 303Gretchen L. Snyder, Joseph P. Hendrick, and AkinoriNishi13 INHIBITION OF PHOSPHODIESTERASES AS A STRATEGY FORTREATMENT OF SPINAL CORD INJURY 353Elena Nikulina and Marie T. FilbinINDEX 375