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Iptakalim: A Potential Antipsychotic Drug with Novel Mechanisms?
Faculty Publications, Department of Psychology
  • Tao Sun, Nanjing Medical University, PR China
  • Changjiu Zhao, University of Nebraska-Lincoln
  • Gang Hu, Nanjing Medical University, PR China
  • Ming Li, University of Nebraska-Lincoln
Date of this Version
1-1-2010
Comments
Published in European Journal of Pharmacology 634:1–3 (May 25, 2010), pp. 68–76; doi: 10.1016/j.ejphar.2010.02.024  Copyright © 2010 Elsevier B.V. Used by permission.
Abstract

Iptakalim is a novel putative adenosine triphosphate (ATP)-sensitive potassium (KATP) channel opener. In the brain, iptakalim is thought to act on the neuronal and astrocytic plasma membrane and/or mitochondrial KATP channels. Because iptakalim demonstrates an action on the regulation of dopamine and glutamate release in the forebrain regions, we examined its potential antipsychotic efficacy in several preclinical tests. First, we show that iptakalim is effective in reducing amphetamine- and phencyclidine-induced hyperlocomotion as well as selectively disrupting conditioned avoidance responding. Next, we show that combined iptakalim and amphetamine treatment produces a reduction on prepulse inhibition of acoustic startle and this combined drug effect is also found with haloperidol, but not with clozapine. Finally, we show that iptakalim and clozapine preferentially increase c-Fos expression in the medial prefrontal cortex, nucleus accumbens and lateral septal nucleus, whereas haloperidol induces a greater increase in the nucleus accumbens, the dorsolateral striatum and lateral septal nucleus. Collectively, our findings indicate that iptakalim is likely to be a potential antipsychotic drug with distinct mechanisms of action. This study also suggests that neuronal and astrocytic plasma membrane and/or mitochondrial KATP channels may be a novel target that deserves attention for antipsychotic drug development. Future research using other sensitive tests is needed to confirm this property of iptakalim.

Citation Information
Tao Sun, Changjiu Zhao, Gang Hu and Ming Li. "Iptakalim: A Potential Antipsychotic Drug with Novel Mechanisms?" (2010)
Available at: http://works.bepress.com/ming_li/3/