Modulation of ion channels in clinical psychopharmacology: adults and younger people

Abstract

This review focuses on the use of Na⁺, Ca²⁺ and Cl^- channel modulators in psychiatric disease. Drugs that modulate ion channels have been used in psychiatry for more than a century, and in this review we critically evaluate clinical research that reports the therapeutic effects of drugs acting on GABA_A, voltage-gated Na⁺ and voltage-gated Ca²⁺ channels in pediatric and adult patients. As in other fields, the evidence underpinning the use of medicines in younger people is far less robust than for adults. In addition, we discuss some current developments and highlight clinical disorders in which current molecules could be further tested. Notable success stories, such as benzodiazepines (in sleep and anxiety disorders) and antiepileptics (in bipolar disorder), have been the result of serendipitous discoveries or refinements of serendipitous discoveries, as in all other major treatments in psychiatry. Genomic, high-throughput screening and molecular pharmacology discoveries may, however, guide further developments in the future. This could include increased research in promising targets that have been perceived as commercially risky, such as selective α-subunit GABA_A receptors.

Keywords::

• anticonvulsant
• Ca²⁺ channel
• Ca²⁺ channel blocker
• GABA agonist
• GABA antagonist
• GABA_A receptor
• membrane transport
• mental disorder
• modulator
• Na⁺ channel

Financial & competing interests disclosure

Dr Malizia has received investigator grants, honoraria or conference hospitality from companies currently identified as GlaxoSmithKline, Lilly, Lundbeck, Merck and Pfizer. He was director of clinical pharmacology at SmithKlineBeecham and has retained those shares and pension arrangements. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.