Egis-11150

A candidate antipsychotic compound with procognitive efficacy in rodents

István Gacsályi, Katalin Nagy, Katalin Pallagi, György Lévay, L. Hársing, Krisztina Móricz, Szabolcs Kertész, Péter Varga, J. Haller, Gábor Gigler, G. Szénási, József Barkóczy, Judit Bíró, Michael Spedding, Ferenc A. Antoni

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Classical antipsychotics, e.g. haloperidol, chlorpromazine, are potent at controlling the positive symptoms of schizophrenia but frequently elicit extrapyramidal motor side-effects. The introduction of atypical antipsychotics such as risperidone, olanzapine and clozapine has obviated this problem, but none of the current drugs seem to improve the cognitive deficits accompanying schizophrenia. Thus there is an unmet need for agents that not only suppress the psychotic symptoms but also ameliorate the impairment of cognition. Here, we report the preclinical properties of a candidate antipsychotic, Egis-11150, that shows marked pro-cognitive efficacy. Egis-11150 displayed high affinity for adrenergic α1, α2c, 5-HT2A 5-HT7, moderate affinity for adrenergic α2a and D2 receptors. It was a functional antagonist on all of the above receptors, with the exception of 5-HT7 receptors, where it was an inverse agonist. Phencyclidine-induced hypermotility in mice and inhibition of conditioned avoidance response in rats were assessed to estimate efficacy against the positive and social withdrawal test in rats was used to predict efficacy against the negative symptoms of schizophrenia. Passive-avoidance learning, novel object recognition and radial maze tests in rats were used to assess pro-cognitive activity, while phencyclidine-induced disruption of prepulse inhibition in mice was examined to test for effects on attention. Egis-11150 (0.01-0.3 mg/kg, ip.) was effective in all of the preclinical models of schizophrenia examined. Moreover, a robust pro-cognitive profile was apparent. In summary, work in preclinical models indicates that Egis-11150 is a potential treatment for controlling the psychosis as well as the cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Original languageEnglish
Pages (from-to)254-263
Number of pages10
JournalNeuropharmacology
Volume64
DOIs
Publication statusPublished - Jan 2013

Fingerprint

Antipsychotic Agents
Rodentia
Schizophrenia
Phencyclidine
olanzapine
Adrenergic Agents
Nootropic Agents
Avoidance Learning
Risperidone
Clozapine
Chlorpromazine
Haloperidol
Psychotic Disorders
Cognition
Pharmaceutical Preparations
Therapeutics

Keywords

  • Antipsychotic pharmacotherapy
  • Atypical antipsychotic
  • Cognitive deficit
  • Phencyclidine
  • Procognitive efficacy
  • Schizophrenia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Egis-11150 : A candidate antipsychotic compound with procognitive efficacy in rodents. / Gacsályi, István; Nagy, Katalin; Pallagi, Katalin; Lévay, György; Hársing, L.; Móricz, Krisztina; Kertész, Szabolcs; Varga, Péter; Haller, J.; Gigler, Gábor; Szénási, G.; Barkóczy, József; Bíró, Judit; Spedding, Michael; Antoni, Ferenc A.

In: Neuropharmacology, Vol. 64, 01.2013, p. 254-263.

Research output: Contribution to journalArticle

Gacsályi, I, Nagy, K, Pallagi, K, Lévay, G, Hársing, L, Móricz, K, Kertész, S, Varga, P, Haller, J, Gigler, G, Szénási, G, Barkóczy, J, Bíró, J, Spedding, M & Antoni, FA 2013, 'Egis-11150: A candidate antipsychotic compound with procognitive efficacy in rodents', Neuropharmacology, vol. 64, pp. 254-263. https://doi.org/10.1016/j.neuropharm.2012.07.017
Gacsályi, István ; Nagy, Katalin ; Pallagi, Katalin ; Lévay, György ; Hársing, L. ; Móricz, Krisztina ; Kertész, Szabolcs ; Varga, Péter ; Haller, J. ; Gigler, Gábor ; Szénási, G. ; Barkóczy, József ; Bíró, Judit ; Spedding, Michael ; Antoni, Ferenc A. / Egis-11150 : A candidate antipsychotic compound with procognitive efficacy in rodents. In: Neuropharmacology. 2013 ; Vol. 64. pp. 254-263.
@article{088d447308bd41208f7ede97177f0608,
title = "Egis-11150: A candidate antipsychotic compound with procognitive efficacy in rodents",
abstract = "Classical antipsychotics, e.g. haloperidol, chlorpromazine, are potent at controlling the positive symptoms of schizophrenia but frequently elicit extrapyramidal motor side-effects. The introduction of atypical antipsychotics such as risperidone, olanzapine and clozapine has obviated this problem, but none of the current drugs seem to improve the cognitive deficits accompanying schizophrenia. Thus there is an unmet need for agents that not only suppress the psychotic symptoms but also ameliorate the impairment of cognition. Here, we report the preclinical properties of a candidate antipsychotic, Egis-11150, that shows marked pro-cognitive efficacy. Egis-11150 displayed high affinity for adrenergic α1, α2c, 5-HT2A 5-HT7, moderate affinity for adrenergic α2a and D2 receptors. It was a functional antagonist on all of the above receptors, with the exception of 5-HT7 receptors, where it was an inverse agonist. Phencyclidine-induced hypermotility in mice and inhibition of conditioned avoidance response in rats were assessed to estimate efficacy against the positive and social withdrawal test in rats was used to predict efficacy against the negative symptoms of schizophrenia. Passive-avoidance learning, novel object recognition and radial maze tests in rats were used to assess pro-cognitive activity, while phencyclidine-induced disruption of prepulse inhibition in mice was examined to test for effects on attention. Egis-11150 (0.01-0.3 mg/kg, ip.) was effective in all of the preclinical models of schizophrenia examined. Moreover, a robust pro-cognitive profile was apparent. In summary, work in preclinical models indicates that Egis-11150 is a potential treatment for controlling the psychosis as well as the cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled 'Cognitive Enhancers'.",
keywords = "Antipsychotic pharmacotherapy, Atypical antipsychotic, Cognitive deficit, Phencyclidine, Procognitive efficacy, Schizophrenia",
author = "Istv{\'a}n Gacs{\'a}lyi and Katalin Nagy and Katalin Pallagi and Gy{\"o}rgy L{\'e}vay and L. H{\'a}rsing and Krisztina M{\'o}ricz and Szabolcs Kert{\'e}sz and P{\'e}ter Varga and J. Haller and G{\'a}bor Gigler and G. Sz{\'e}n{\'a}si and J{\'o}zsef Bark{\'o}czy and Judit B{\'i}r{\'o} and Michael Spedding and Antoni, {Ferenc A.}",
year = "2013",
month = "1",
doi = "10.1016/j.neuropharm.2012.07.017",
language = "English",
volume = "64",
pages = "254--263",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Egis-11150

T2 - A candidate antipsychotic compound with procognitive efficacy in rodents

AU - Gacsályi, István

AU - Nagy, Katalin

AU - Pallagi, Katalin

AU - Lévay, György

AU - Hársing, L.

AU - Móricz, Krisztina

AU - Kertész, Szabolcs

AU - Varga, Péter

AU - Haller, J.

AU - Gigler, Gábor

AU - Szénási, G.

AU - Barkóczy, József

AU - Bíró, Judit

AU - Spedding, Michael

AU - Antoni, Ferenc A.

PY - 2013/1

Y1 - 2013/1

N2 - Classical antipsychotics, e.g. haloperidol, chlorpromazine, are potent at controlling the positive symptoms of schizophrenia but frequently elicit extrapyramidal motor side-effects. The introduction of atypical antipsychotics such as risperidone, olanzapine and clozapine has obviated this problem, but none of the current drugs seem to improve the cognitive deficits accompanying schizophrenia. Thus there is an unmet need for agents that not only suppress the psychotic symptoms but also ameliorate the impairment of cognition. Here, we report the preclinical properties of a candidate antipsychotic, Egis-11150, that shows marked pro-cognitive efficacy. Egis-11150 displayed high affinity for adrenergic α1, α2c, 5-HT2A 5-HT7, moderate affinity for adrenergic α2a and D2 receptors. It was a functional antagonist on all of the above receptors, with the exception of 5-HT7 receptors, where it was an inverse agonist. Phencyclidine-induced hypermotility in mice and inhibition of conditioned avoidance response in rats were assessed to estimate efficacy against the positive and social withdrawal test in rats was used to predict efficacy against the negative symptoms of schizophrenia. Passive-avoidance learning, novel object recognition and radial maze tests in rats were used to assess pro-cognitive activity, while phencyclidine-induced disruption of prepulse inhibition in mice was examined to test for effects on attention. Egis-11150 (0.01-0.3 mg/kg, ip.) was effective in all of the preclinical models of schizophrenia examined. Moreover, a robust pro-cognitive profile was apparent. In summary, work in preclinical models indicates that Egis-11150 is a potential treatment for controlling the psychosis as well as the cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

AB - Classical antipsychotics, e.g. haloperidol, chlorpromazine, are potent at controlling the positive symptoms of schizophrenia but frequently elicit extrapyramidal motor side-effects. The introduction of atypical antipsychotics such as risperidone, olanzapine and clozapine has obviated this problem, but none of the current drugs seem to improve the cognitive deficits accompanying schizophrenia. Thus there is an unmet need for agents that not only suppress the psychotic symptoms but also ameliorate the impairment of cognition. Here, we report the preclinical properties of a candidate antipsychotic, Egis-11150, that shows marked pro-cognitive efficacy. Egis-11150 displayed high affinity for adrenergic α1, α2c, 5-HT2A 5-HT7, moderate affinity for adrenergic α2a and D2 receptors. It was a functional antagonist on all of the above receptors, with the exception of 5-HT7 receptors, where it was an inverse agonist. Phencyclidine-induced hypermotility in mice and inhibition of conditioned avoidance response in rats were assessed to estimate efficacy against the positive and social withdrawal test in rats was used to predict efficacy against the negative symptoms of schizophrenia. Passive-avoidance learning, novel object recognition and radial maze tests in rats were used to assess pro-cognitive activity, while phencyclidine-induced disruption of prepulse inhibition in mice was examined to test for effects on attention. Egis-11150 (0.01-0.3 mg/kg, ip.) was effective in all of the preclinical models of schizophrenia examined. Moreover, a robust pro-cognitive profile was apparent. In summary, work in preclinical models indicates that Egis-11150 is a potential treatment for controlling the psychosis as well as the cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

KW - Antipsychotic pharmacotherapy

KW - Atypical antipsychotic

KW - Cognitive deficit

KW - Phencyclidine

KW - Procognitive efficacy

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=84866373031&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866373031&partnerID=8YFLogxK

U2 - 10.1016/j.neuropharm.2012.07.017

DO - 10.1016/j.neuropharm.2012.07.017

M3 - Article

VL - 64

SP - 254

EP - 263

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -