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Discovery of potential antipsychotic agents possessing pro-cognitive properties

Lameh, Jelveh ; McFarland, Krista ; Ohlsson, Jorgen ; Ek, Fredrik LU ; Piu, Fabrice ; Burstein, Ethan S. ; Tabatabaei, Ali ; Olsson, Roger LU ; Bradley, Stefania Risso and Bonhaus, Douglas W. (2012) In Naunyn-Schmiedeberg's Archives of Pharmacology 385(3). p.313-323
Abstract

Current antipsychotic drug therapies for schizophrenia have limited efficacy and are notably ineffective at addressing the cognitive deficits associated with this disorder. The present study was designed to develop effective antipsychotic agents that would also ameliorate the cognitive deficits associated with this disease. In vitro studies comprised of binding and functional assays were utilized to identify compounds with the receptor profile that could provide both antipsychotic and pro-cognitive features. Antipsychotic and cognitive models assessing in vivo activity of these compounds included locomotor activity assays and novel object recognition assays. We developed a series of potential antipsychotic agents with a novel receptor... (More)

Current antipsychotic drug therapies for schizophrenia have limited efficacy and are notably ineffective at addressing the cognitive deficits associated with this disorder. The present study was designed to develop effective antipsychotic agents that would also ameliorate the cognitive deficits associated with this disease. In vitro studies comprised of binding and functional assays were utilized to identify compounds with the receptor profile that could provide both antipsychotic and pro-cognitive features. Antipsychotic and cognitive models assessing in vivo activity of these compounds included locomotor activity assays and novel object recognition assays. We developed a series of potential antipsychotic agents with a novel receptor activity profile comprised of muscarinic M 1 receptor agonism in addition to dopamine D 2 antagonism and serotonin 5-HT 2A inverse agonism. Like other antipsychotic agents, these compounds reverse both amphetamine and dizocilpine-induced hyperactivity in animals. In addition, unlike other antipsychotic drugs, these compounds demonstrate pro-cognitive actions in the novel object recognition assay. The dual attributes of antipsychotic and pro-cognitive actions distinguish these compounds from other antipsychotic drugs and suggest that these compounds are prototype molecules in the development of novel procognitive antipsychotic agents.

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Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antipsychotic drug (APD), Dopamine antagonism, Muscarinic agonism, Schizophrenia, Serotonin antagonism
in
Naunyn-Schmiedeberg's Archives of Pharmacology
volume
385
issue
3
pages
11 pages
publisher
Springer
external identifiers
  • pmid:22083558
  • scopus:84862895922
ISSN
0028-1298
DOI
10.1007/s00210-011-0702-2
language
English
LU publication?
no
id
afe7691b-e9d8-4616-b1d1-ae9d879f15c7
date added to LUP
2019-10-02 10:57:52
date last changed
2020-01-13 02:26:19
@article{afe7691b-e9d8-4616-b1d1-ae9d879f15c7,
  abstract     = {<p>Current antipsychotic drug therapies for schizophrenia have limited efficacy and are notably ineffective at addressing the cognitive deficits associated with this disorder. The present study was designed to develop effective antipsychotic agents that would also ameliorate the cognitive deficits associated with this disease. In vitro studies comprised of binding and functional assays were utilized to identify compounds with the receptor profile that could provide both antipsychotic and pro-cognitive features. Antipsychotic and cognitive models assessing in vivo activity of these compounds included locomotor activity assays and novel object recognition assays. We developed a series of potential antipsychotic agents with a novel receptor activity profile comprised of muscarinic M <sub>1</sub> receptor agonism in addition to dopamine D <sub>2</sub> antagonism and serotonin 5-HT <sub>2A</sub> inverse agonism. Like other antipsychotic agents, these compounds reverse both amphetamine and dizocilpine-induced hyperactivity in animals. In addition, unlike other antipsychotic drugs, these compounds demonstrate pro-cognitive actions in the novel object recognition assay. The dual attributes of antipsychotic and pro-cognitive actions distinguish these compounds from other antipsychotic drugs and suggest that these compounds are prototype molecules in the development of novel procognitive antipsychotic agents.</p>},
  author       = {Lameh, Jelveh and McFarland, Krista and Ohlsson, Jorgen and Ek, Fredrik and Piu, Fabrice and Burstein, Ethan S. and Tabatabaei, Ali and Olsson, Roger and Bradley, Stefania Risso and Bonhaus, Douglas W.},
  issn         = {0028-1298},
  language     = {eng},
  month        = {03},
  number       = {3},
  pages        = {313--323},
  publisher    = {Springer},
  series       = {Naunyn-Schmiedeberg's Archives of Pharmacology},
  title        = {Discovery of potential antipsychotic agents possessing pro-cognitive properties},
  url          = {http://dx.doi.org/10.1007/s00210-011-0702-2},
  doi          = {10.1007/s00210-011-0702-2},
  volume       = {385},
  year         = {2012},
}