Which molecular mechanism best explains the mood-stabilising action of lithium?
- A Inhibition of glycogen synthase kinase-3 beta and inositol monophosphatase, depleting intracellular inositol ✓
- B Allosteric potentiation of GABA-A chloride channels
- C Blockade of dopamine D2 receptors in the mesolimbic pathway
- D Irreversible inhibition of cyclooxygenase-2 in glial cells
Correct answer: A. Inhibition of glycogen synthase kinase-3 beta and inositol monophosphatase, depleting intracellular inositol
Explanation
Lithium acts through two accepted mechanisms: inhibition of glycogen synthase kinase-3 beta, affecting neuroplasticity and circadian gene expression, and inhibition of inositol monophosphatase, which depletes free inositol and dampens phosphatidylinositol second messenger signalling (the inositol depletion hypothesis). GABA-A potentiation is the action of benzodiazepines, D2 blockade defines antipsychotics, and COX-2 inhibition belongs to anti-inflammatory drugs. These mechanisms underlie both its antimanic effect and its neuroprotective profile.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.