A review of the preclinical and clinical evidence for protein kinase C as a target for drug development for bipolar disorder.
In this article, we review preclinical studies investigating the role of protein kinase C (PKC) as it pertains to mania and effective antimanic agents. We then discuss clinical studies conducted with tamoxifen, a relatively selective PKC inhibitor, in acute bipolar mania. We conclude that PKC is an important target-arguably the first mechanistically distinct drug target for bipolar disorder. PKC holds considerable promise as a novel target for developing a new line of treatments for bipolar disorder.
DiazGranados
Nancy
N
Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, 10 Center Drive, CRC, Unit 7 Southeast, Room 7-3445, Bethesda, MD 20892, USA.
Zarate
Carlos A
CA
D000328:Adult; D000818:Animals; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000201:enzymology; D001921:Brain / Q000187:drug effects; D018849:Controlled Clinical Trials as Topic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004359:Drug Therapy, Combination; D015507:Drugs, Investigational / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013629:Tamoxifen / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use
D018692:Antimanic Agents; D015507:Drugs, Investigational; D013629:Tamoxifen; D016651:Lithium Carbonate; D014635:Valproic Acid; D011493:Protein Kinase C