Iptakalim: A potential antipsychotic drug with novel mechanisms?

Tao Sun, Changjiu Zhao, Gang Hu, Ming Li

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)68-76
Number of pages9
JournalEuropean Journal of Pharmacology
Volume634
Issue number1-3
DOIs
StatePublished - May 1 2010

Fingerprint

Antipsychotic Agents
Septal Nuclei
Clozapine
Nucleus Accumbens
Haloperidol
Amphetamine
Cell Membrane
Phencyclidine
KATP Channels
N-(1-methylethyl)-1,1,2-trimethylpropylamine
Potassium Channels
Prosencephalon
Prefrontal Cortex
Acoustics
Glutamic Acid
Dopamine
Adenosine Triphosphate
Brain
Pharmaceutical Preparations

Keywords

  • Amphetamine
  • Antipsychotic drug
  • C-Fos
  • Conditioned avoidance response
  • Iptakalim
  • K channel
  • Phencyclidine
  • Prepulse inhibition

ASJC Scopus subject areas

  • Pharmacology

Cite this

Iptakalim : A potential antipsychotic drug with novel mechanisms? / Sun, Tao; Zhao, Changjiu; Hu, Gang; Li, Ming.

In: European Journal of Pharmacology, Vol. 634, No. 1-3, 01.05.2010, p. 68-76.

Research output: Contribution to journalArticle

Sun, Tao ; Zhao, Changjiu ; Hu, Gang ; Li, Ming. / Iptakalim : A potential antipsychotic drug with novel mechanisms?. In: European Journal of Pharmacology. 2010 ; Vol. 634, No. 1-3. pp. 68-76.
@article{0157e53e0b7f4312905749caac621890,
title = "Iptakalim: A potential antipsychotic drug with novel mechanisms?",
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.",
keywords = "Amphetamine, Antipsychotic drug, C-Fos, Conditioned avoidance response, Iptakalim, K channel, Phencyclidine, Prepulse inhibition",
author = "Tao Sun and Changjiu Zhao and Gang Hu and Ming Li",
year = "2010",
month = "5",
day = "1",
doi = "10.1016/j.ejphar.2010.02.024",
language = "English (US)",
volume = "634",
pages = "68--76",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Iptakalim

T2 - A potential antipsychotic drug with novel mechanisms?

AU - Sun, Tao

AU - Zhao, Changjiu

AU - Hu, Gang

AU - Li, Ming

PY - 2010/5/1

Y1 - 2010/5/1

N2 - 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.

AB - 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.

KW - Amphetamine

KW - Antipsychotic drug

KW - C-Fos

KW - Conditioned avoidance response

KW - Iptakalim

KW - K channel

KW - Phencyclidine

KW - Prepulse inhibition

UR - http://www.scopus.com/inward/record.url?scp=77951206390&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951206390&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2010.02.024

DO - 10.1016/j.ejphar.2010.02.024

M3 - Article

C2 - 20184878

AN - SCOPUS:77951206390

VL - 634

SP - 68

EP - 76

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

ER -