Biochemical and Pharmacological Roles of Adenosylmethionine and the Central Nervous System contains the proceedings of an International Round Table on Adenosylmethionine and the Central Nervous System held in Naples, Italy, on May 2, 1978. The papers explore the biochemical and pharmacological roles of S-adenosylmethionine (SAM), with particular emphasis on its functions in the central nervous system (CNS). This book consists of 13 chapters and opens with an introduction to some novel biochemical aspects of SAM and related sulfur compounds, paying particular attention to transmethylation reactions; polyamine biosynthesis and unusual biological roles of adenosylmethionine; metabolic pathways related to adenosine-sulfur compounds; and transport of adenosylmethionine. The following chapters discuss a number of chemical and biochemical properties of SAM as well as its pharmacological aspects within the CNS. The relation between folate and adenosylmethionine metabolism in the brain is examined, along with the effect of SAM administration on noradrenaline and serotonin metabolism in rat brain; cerebral utilization of adenosylmethionine and adenosylhomocysteine; and antidepressant effects of adenosylmethionine. Methylation in schizophrenia is also considered. This monograph will be a valuable source of information for biochemists and pharmacologists.

First multi-year cumulation covers six years: 1965-70.

V M. ANDREOLl, A. AGNOLI, and C. FAZIO The transfer of a methyl group from a donor to an acceptor compound is a fundamental biochemie al process long since known to biologists; the process is involved, for instance, in the metabolism of porphyrins, nuc1eic acids, and fatty acids. Only recently, however, did transmethylation processes reveal their decisive role in CNS biochemistry - namely with the discovery that such processes are linked with the biogenie amines that have been conc1usively identified as the chemical mediators of neu ronal transmission and, more broadly, of behavior. The first suggestion that transmethylation processes might be involved in the origina tion of certain mental diseases came from Harley-Mason (1952), who noticed that many of the hallucinogenic substances known at that time contained methyl radicals, and par ticularly that mescaline represented the product of O-methylation of dopamine in posi tions 3, 4, and 5. This hypothesis was put forward when the O-methylation of catechol amines by catechol-O-methyltransferases had not yet been described. Harley-Mason further proposed that in the living organism the process of O-methyla tion might follow a "deviant" metabolie pathway, and that the accumulation of abnor mal methylated metabolites endowed with hallucinogenic properties might be responsi ble for the implementation of some mental diseases, notably schizophrenia. He also called attention to a substance, 3,4-dimethoxyphenylethylamine (3,4-DMPEA) as a possible psychotogenic moleeule, on the strength of its capacity for producing cata tonia in experimental animals

This book has been developed from its earlier and far less formal presentment as the proceedings of a symposium entitled The Biochemistry of S-Adenosylmethionine as a Basis for Drug Design that was held at the Solstrand Fjord Hotel in Bergen, Norway on June 30-July 4, 1985. The purpose of the symposium was to bring together scientists from various disciplines (biochemistry, pharmacology, virology, immunology, chemistry, medicine, and so on) to discuss the recent advances that have been made in our understanding of the biological roles of S adenosylmethionine (AdoMet) and to discuss the feasibility of utilizing AdoMet-dependent enzymes as targets for drug design. Thus the information provided herein will be of value not only to basic scientists involved in elucidating the role of AdoMet in biology, but also to medicinal chemists who are using this basic knowledge in the process of drug design. The volume should also be of interest to pharmacologists and clinicians involved in biological evaluation of potential therapeutic agents arising from the efforts of the biochemists and medicinal chemists. Each plenary speaker at the symposium was requested to submit a chapter reviewing recent contributions of their discipline to our base of knowledge about the biological role of AdoMet. Topics covered in this volume include protein and phospholipid methylations (Section A), nucleic acid methyl ations (Section B), the regulation of AdoMet, S-adenosylhomocysteine, and methylthioadenosine metabolism (Section C), clinical aspects of AdoMet (Section D), and the design, synthesis, and biological evaluation of trans methylation inhibitors (Section E).