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Acute mania is treated with antipsychotics and with mood stabilizers (lithium and the anticonvulsants valproate and carbamazepine). Identifying the biochemical targets of these medications has been challenging. A recent hypothesis is that the protein kinase C (PKC) signaling cascade is a target of the mood stabilizers. This is supported by gene studies and animal models, suggesting that PKC activation is associated with mania-like behavior. PKC inhibitors block acute responses to cocaine and reduce risk-taking behavior. Tamoxifen, a nonsteroidal antiestrogen used to treat breast cancer, is a potent and selective PKC inhibitor that crosses the blood-brain barrier.
Investigators previously conducted a single-blind study of tamoxifen in acute m…