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  • Title: Mood stabilizers: shared mechanisms of action at postsynaptic signal-transduction and kindling processes.
    Author: Stoll AL, Severus WE.
    Journal: Harv Rev Psychiatry; 1996; 4(2):77-89. PubMed ID: 9384977.
    Abstract:
    Several distinct classes of agents have demonstrated efficacy as mood stabilizers in patients with bipolar disorder. It may be reasonable to assume that these agents share one or more common mechanisms of action. This paper will explore the hypothesis that all effective mood stabilizers exert their actions through inhibition of postsynaptic signal-transduction and kindling processes. A literature search was performed for all currently used mood stabilizers to identify reports of mood-stabilizer action in postreceptor cell-signaling and kindling processes. Most effective mood stabilizers appear to inhibit intracellular calcium mobilization through several distinct mechanisms. In addition, several mood stabilizers appear to diminish generation of second-messenger molecules from the membrane phospholipids phosphatidylinositol and phosphatidylcholine, inhibit the activity of protein kinases, and directly inhibit activity of G-proteins. Finally, all established mood stabilizers also exhibit antikindling effects. All of these mechanisms of action could dampen excessive intracellular and intercellular signaling, which may be a core feature of the pathophysiology of bipolar disorder. The observation that all effective mood stabilizers inhibit both kindling and signal-transduction pathways suggests that these processes are intimately linked. We hypothesize that an effective mood stabilizer must possess some specific minimum inhibitory effects at postsynaptic signal-transduction and kindling processes. If this hypothesis is correct, then a rational search for safer and more effective mood-stabilizing agents can begin.
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