neuronal Nicotinic Receptors. Pharmacology and Therapeutic Opportunities

American Journal of Pharmaceutical Education, Summer 1999 by Maickel, Roger P

STEPHEN P. AARNERIC & JORGE D. BRIONI. Neuronal Nicotinic Receptors. Pharmacology and Therapeutic Opportunities. New York, NY. John Wiley & Sons Inc., 1999, xii 421 pp., 84 figs., 12 tbls., $175.00.

Despite the fact that neurotransmission via cholinergic systems extends back to some of the earliest days of pharmacology, the nicotinic acetylcholine receptor (nAChR) has not been a major target for research efforts aimed at the development of therapeutic interventions. Indeed, with the exception of studies targeted towards the development of approaches to treat the "addiction" of tobacco usage, little has been done to examine body systems involving nAChR functions in sharp contrast to volumes of work on the muscarinic ACh systems. This volume attempts to fill at least part of this void, to bring the current state of knowledge of the nAChR up to date, and to project possible clinical therapeutic applications into the future.

The first section of the volume consists of 6 chapters, beginning with a detailed description of the isolation, purification and cloning of the nAChR and continuing with a thorough detailing of the transcriptional regulation, biochemical and biophysical characterization and structural and functional aspects of the post-synaptic neuronal events, including regulation and desensitization. This section concludes with an overview of the various cell lines available for use as model systems to facilitate nAChR research and an effective summary of the various ways in which such receptors are expressed in human tissues.

The next section (five chapters) addresses the physiological roles of systems involving the nAChR, beginning with some of the better known aspects of such systems in the mammalian brain, and continuing through potential roles in neurotransmitter release modulation and biological functioning. Particular emphasis is placed on the wide diversity of such functions at both organ and subcellular levels. The concluding chapter of this portion of the volume addresses two newer areas of interest, namely immunosuppression and anti-inflammatory actions of nicotinic agonists.

Sections III and IV consist of two chapters each and overview the overall chemical pharmacology of substances acting upon various nAChR systems. The compounds considered include natural products and synthetic medicinals. The aspects covered range from pharmacokinetic characteristics to structure-activity relationships. These sections are replete with numerous illustrations of collected data as well as metabolic pathways and structural-chemical displays. They form the basis for the various projections for future applications of knowledge of the nAChR included in the remainder of the volume.

The final section of this book consists of eight chapters pointing towards potential future developments in clinical pharmacology and therapeutics involving agents directed at interactions with nAChRs in various body systems. Some of these potential targets are obvious, such as aids to cessation of cigarette smoking. Others, such as the treatment of convulsive disorders and relief of pain, are presently less apparent. Several chapters deal with potential for such therapeutic targets as attention deficit disorders and other psychotropic problems.

In summary, this volume should be an extremely important addition to any library collection of reference volumes in pharmacology. It will form the basis for several decades of future research. The individual chapters are profusely illustrated, replete with useful data presentations, and well documented with up-to-date references. The style of presentation is clear and thorough with carefully blended aspects of basic science and projections for possible clinical applications.

Roger P. Maickel

Purdue University