Do Lithium and Anticonvulsants Target the Brain Arachidonic Acid Cascade in Bipolar Disorder?

2002 ◽  
Vol 59 (7) ◽  
pp. 592 ◽  
Author(s):  
Stanley I. Rapoport ◽  
Francesca Bosetti
Keyword(s):  
Bipolar Disorder ◽  
Arachidonic Acid ◽  
Arachidonic Acid Cascade ◽  
The Brain

Is the brain arachidonic acid cascade a common target of drugs used to manage bipolar disorder?

2009 ◽  
Vol 37 (5) ◽  
pp. 1104-1109 ◽  
Author(s):  
Richard P. Bazinet
Keyword(s):  
Bipolar Disorder ◽  
Valproic Acid ◽  
Arachidonic Acid ◽  
Rat Brain ◽  
Bipolar Depression ◽  
Chronic Administration ◽  
Mood Stabilizers ◽  
Arachidonic Acid Cascade ◽  
Brain Phospholipids ◽  
The Brain

Although lithium has been used therapeutically to treat patients with bipolar disorder for over 50 years, its mechanism of action, as well as that of other drugs used to treat bipolar disorder, is not agreed upon. In the present paper, I review studies in unanaesthetized rats using a neuropharmacological approach, combined with kinetic, biochemical and molecular biology techniques, demonstrating that chronic administration of three commonly used mood stabilizers (lithium, valproic acid and carbamazepine), at therapeutically relevant doses, selectively target the brain arachidonic acid cascade. Upon chronic administration, lithium and carbamazepine decrease the binding activity of activator protein-2 and, in turn, the transcription, translation and activity of its arachidonic acid-selective calcium-dependent phospholipase A2 gene product, whereas chronic valproic acid non-competitively inhibits long-chain acyl-CoA synthetase. The net overlapping effects of the three mood stabilizers are decreased turnover of arachidonic acid, but not of docosahexaenoic acid, in rat brain phospholipids, as well as decreased brain cyclo-oxygenase-2 and prostaglandin E2. As an extension of this theory, drugs that are thought to induce switching to mania, especially when administered during bipolar depression (fluoxetine and imipramine), up-regulate enzymes of the arachidonic acid cascade and turnover of arachidonic acid in rat brain phospholipids. Future basic and clinical studies on the arachidonic acid hypothesis of bipolar disorder are warranted.

Arachidonic acid cascade in endothelial pathobiology

2005 ◽  
Vol 69 (3) ◽  
pp. 107-127 ◽  
Author(s):  
Natalia V. Bogatcheva ◽  
Marina G. Sergeeva ◽  
Steven M. Dudek ◽  
Alexander D. Verin
Keyword(s):  
Arachidonic Acid ◽  
Arachidonic Acid Cascade

scholarly journals The role of the arachidonic acid cascade in the hypotensive activity of N-(dibenzyloxyphosphinoyl)-L-alanyl-L-prolyl-L-proline

1986 ◽  
Vol 40 ◽  
pp. 233
Author(s):  
Ryota Yoshimoto ◽  
Toshihiko Ishimitsu ◽  
Yoshikatsu Koyama ◽  
Shigebumi Hashimoto ◽  
Hiroaki Matsuoka ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Hypotensive Activity ◽  
Arachidonic Acid Cascade
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