title: Tamoxifen and amphetamine abuse: Are there therapeutic possibilities?
abstract: Although best known as a selective estrogen receptor modulator (SERM), tamoxifen is a drug with a wide range of activities. Tamoxifen has demonstrated some efficacy has a therapeutic for bipolar mania and is believed to exert these effects through inhibition of protein kinase C (PKC). As the symptoms of amphetamine treatment in rodents are believed to mimic the symptoms of a manic episode, many of the preclinical studies for this indication have demonstrated that tamoxifen inhibits amphetamine action. The amphetamine-induced increase in extracellular dopamine which gives rise to the 'manic' effects is due to interaction of amphetamine with the dopamine transporter. We and others have demonstrated that PKC reduces amphetamine-induced reverse transport through the dopamine transporter. In this review, we will outline the actions of tamoxifen as a SERM and further detail another known action of tamoxifen-inhibition of PKC. We will summarize the literature showing how tamoxifen affects amphetamine action. Finally, we will present our hypothesis that tamoxifen, or an analog, could be used therapeutically to reduce amphetamine abuse in addition to treating mania.
authors: Department of Pharmacology, 2220E MSRB III, 1150 West Medical Center Drive, University of Michigan Medical School, Ann Arbor, MI 28109-5632, United States.
authors: Sarah
authors: S
authors: Mikelman
authors: Department of Pharmacology, 2220E MSRB III, 1150 West Medical Center Drive, University of Michigan Medical School, Ann Arbor, MI 28109-5632, United States.
authors: Natalie
authors: N
authors: Mardirossian
authors: Department of Pharmacology, 2220E MSRB III, 1150 West Medical Center Drive, University of Michigan Medical School, Ann Arbor, MI 28109-5632, United States. Electronic address: pgnegy@umich.edu.
authors: Margaret E
authors: ME
authors: Gnegy
mesh_terms: D019969:Amphetamine-Related Disorders / Q000188:drug therapy*; D000818:Animals; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D013629:Tamoxifen; D011493:Protein Kinase C
keywords: Amphetamine; Bipolar mania; Dopamine; Protein kinase C; Tamoxifen