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Role of Inositol in the Treatment of Psychiatric Disorders

Basic and Clinical Aspects

Summary

Myo-inositol is a ubiquitous carbohydrate that is present in large amounts in brain tissue and is involved in neuronal signalling and osmoregulation. This sugar is an essential component of the inositol signalling system, which is a post-receptor second messenger signalling system found in many cells. Myo-inositol is the precursor of membrane inositol phospholipids, which are critically linked to a number of CNS receptor signalling systems, including muscarinic, serotonergic, adrenergic, metabotropic and histaminergic systems, and those linked to cholecystokinin, tachykinins, neurotensin, platelet activating factor and other transmitters.

Upon stimulation of these receptors, a signal is transmitted through a guanosine triphosphate (GTP)-binding protein (Gq), which then activates the enzyme phospholipase C. This results in the release of a second messenger, inositol 1,4,5-trisphosphate (InsP3), from membrane inositol phospholipids. InsP3 then causes the release of free intracellular calcium into the cytosol, activating a number of enzymes or receptors.

Myo-inositol in the brain is derived from 3 sources: (i) receptor stimulation (a salvage pathway); (ii) de novo synthesis from glucose; and (iii) uptake of dietary myo-inositol through plasma membrane myo-inositol transporters. Most myo-inositol is probably derived from the first 2 sources, which are controlled through the lithium-sensitive enzyme myo-inositol monophosphatase (IMPase). This enzyme acts upon myo-inositol monophosphates, hydrolysing them to release free myo-inositol. Recent biochemical, molecular and crystallographic studies have demonstrated that the overall metabolism of brain inositol is closely modulated by this enzyme. Lithium salts, which are commonly used in various psychiatric conditions, inhibit this enzyme, and this action has been implicated as a therapeutic mechanism of action of lithium.

A change in the availability of CNS inositol may lead to altered brain cell signalling pathways and, eventually, to the development of a neuropsychiatric disorder. Recent evidence indicates that myo-inositol has psychoactive effects, with initial studies demonstrating effectiveness in the treatment of depression, panic disorder and obsessive-compulsive disorder. At present, the exact mechanism of these clinical effects is uncertain. The development of various inositol system-based drugs may lead to future psychoactive drugs designed to modulate a second messenger cascade of events rather than a receptor system, and will lead to further understanding of CNS disease from a post-receptor second messenger perspective.

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Correspondence to Dr Robert Vadnal.

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Vadnal, R., Parthasarathy, L. & Parthasarathy, R. Role of Inositol in the Treatment of Psychiatric Disorders. CNS Drugs 7, 6–16 (1997). https://doi.org/10.2165/00023210-199707010-00002

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Keywords

  • Inositol
  • Panic Disorder
  • BioI Psychiatry
  • Sitol
  • Inositol Lipid