Pharmacology for Chemists: Drug Discovery in Context
5: Actions of Drugs on The Brain and CNS Disorders
Published:25 Oct 2017
Special Collection: RSC eTextbook CollectionProduct Type: Textbooks
T. P. Blackburn, in Pharmacology for Chemists: Drug Discovery in Context, ed. R. Hill, T. Kenakin, and T. Blackburn, The Royal Society of Chemistry, 2017, pp. 130-220.
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The psychiatric and neurological drugs reviewed in this section include anxiolytics, antidepressants, antipsychotics, sedative-hypnotics, anticonvulsants, and general and local anaesthetics. The pharmacology and chemistry for various classes of CNS drugs show several commonalities. For example, sedative-hypnotics also possess anxiolytic and anticonvulsant properties and at higher concentrations are general anaesthetics. Antipsychotics, also possess sedative-like/anxiolytic properties, but are unique in that they ameliorate the positive or negative thought disorders of schizophrenia. The structural similarities of the many CNS compounds are associated with allosteric or nonspecific binding to receptor proteins, where hydrophobic groups attach to a semipolar group that are capable of acting as a protein donor or acceptor – a common structural chemotype with CNS agents, that has stymied therapeutic advances over recent decades, thus, accelerating the need for breakthrough innovative approaches in medicinal chemistry, neuropharmacology/neuroscience and the formation of international collaborations like the Human Brain Project. This project, together with significant advances in imaging technologies (e.g. optogenetics – which uses light to control neurones in the brain) and gene editing (CRISPR/Cas9), are game changes in our understanding of how CNS agents interact with neurotransmitters, neuronal brain circuits, to unmask specific pathophysiological states associated with CNS disorders and pave the way for the development of new psychiatric and neurological drugs over the next decade. This chapter reviews recent progress in neuropharmacology for several CNS disease targets.