The 'inositol depletion hypothesis' explains lithium's mood-stabilizing action through which specific enzymatic inhibition?

• A Inhibition of adenylyl cyclase, lowering cAMP generation throughout the limbic system
• B Inhibition of glycogen synthase kinase-3 beta, blocking IP3 receptor signaling
• C Inhibition of phospholipase C, preventing formation of IP3 and DAG at the membrane
• D Uncompetitive inhibition of inositol monophosphatase, depleting free inositol needed to resynthesize phosphatidylinositol second messengers ✓

Explanation

Lithium uncompetitively inhibits inositol monophosphatase, blocking recycling of inositol phosphate back to free inositol. Active neurons relying heavily on PI-cycle signaling become depleted of inositol and cannot resynthesize PIP2-derived second messengers IP3 and DAG, dampening overactive circuits. Inhibition of glycogen synthase kinase-3 beta is a separate, complementary mechanism and does not explain inositol depletion itself.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.