5HT2C Receptors in the Pathophysiology of CNS Disease
Article first published online: 9 NOV 2011
© 2011 The Author. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 72, Issue 6, page 1002, December 2011
How to Cite
Hill, R. G. (2011), 5HT2C Receptors in the Pathophysiology of CNS Disease. British Journal of Clinical Pharmacology, 72: 1002. doi: 10.1111/j.1365-2125.2011.04033.x
- Issue published online: 9 NOV 2011
- Article first published online: 9 NOV 2011
- Accepted manuscript online: 8 JUN 2011 01:02AM EST
- RECEIVED; 1 January 2011; ACCEPTED; 1 January 2011; ACCEPTED ARTICLE; 8 June 2011
5HT2C Receptors in the Pathophysiology of CNS Disease . Giuseppe Di Giovanni, Ennio Esposito, Vincenzo Di Matteo ( Editors ). Published by Humana Press , New York , 2011 . 557 pages, hardback $239. ISBN 978-1-60761-940-6 .
I remember the debate in the 1960s and 1970s as to whether there were two or three 5-HT (serotonin) receptors and was an interested spectator to the subsequent explosion in molecular pharmacology that led to our current tally of 14 receptors for 5-HT reliably characterized by expression cloning. The maturity of this field of study today is well illustrated by this book, where 557 pages are devoted to a summary of our state of knowledge of just one of these receptors. The book is well presented, with good use of diagrams, some in colour, although micrographs suffer from being reproduced on matt rather than glossy paper. In the main it is suitably up to date, with many citations from the 2010 literature, although a few chapters had clearly been longer in gestation. There is a good mix of international authors, with acknowledged leaders in the field being responsible for some key chapters.
The book opens with a chapter on the history of the discovery of the 5HT2C receptor some 25 years ago by a traditional pharmacology approach at the then Sandoz laboratories in Basle. Initially called the 5-HT1C receptor on the basis of ligand-binding studies, it was renamed 5HT2C after its second messenger was found to be the phospholipase C cascade and expression cloning revealed a family resemblance to the other 5-HT2 receptors. Subsequent chapters describe the widespread but heterogeneous distribution of the 5HT2C receptor in the brain, with good evidence emerging for a role in modulating the dopamine pathways. The special features of the receptor are given suitable prominence, revealing that this is one of the small number of G-protein-coupled receptors that displays constitutive activity and is subject to RNA editing during its expression. The hot topic of receptor dimerization also receives a mention, although it is not yet clear whether this is a property of the 5HT2C receptor in vivo. It is pleasing to find a chapter devoted to the medicinal chemistry of 5HT2C ligands, explaining the challenge of making molecules that adequately distinguish between 5HT2A, 5HT2B and 5HT2C receptors. The use of transgenic animals, in particular 5HT2C−/− mice, in order to help elucidate the diverse physiological functions of this receptor is also comprehensively described. There is a succession of interesting chapters dealing with the possible role of the receptor in depression, schizophrenia, addiction, eating behaviour, dyskinesias, sleep, epilepsy, cognition, Alzheimer's disease and ocular hypotension. For the non-expert, it would have been valuable to have followed these with an expert summary that attempted to put all of this in context and point out the areas of most likely clinical relevance. As it was, the book was left open ended, which may not be an issue if it is intended only for the bookshelves of the cognoscenti.
In summary, this is a useful book describing the properties of a receptor that may well turn out to be a therapeutically important drug target, with selective ligands already being evaluated in phase II trials for control of appetite. However, the high price of the book and the lack of a concluding summary chapter may restrict it to use by experts in the field.