Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior.

Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior. Abstract Text:

A C Arai,M Kessler,

Ampakines are drugs structurally derived from aniracetam that potentiate currents mediated by AMPA type glutamate receptors. These drugs slow deactivation and attenuate desensitization of AMPA receptor currents, increase synaptic responses and enhance long-term potentiation. This review focuses mainly on recent physiological studies and on evidence for two distinct subfamilies. Type I compounds like CX546 are very effective in prolonging synaptic responses while type II compounds like CX516 mainly increase response amplitude. Type I and II drugs do not compete in binding assays and thus presumably act through separate sites. Their differences are likely to have consequences also for synaptic plasticity and behavior. Thus, while all ampakines facilitated long-term potentiation, only CX546 enhanced long-term depression. Further discussed are studies showing that ampakine effects vary substantially between neurons, with increases in EPSCs being larger in CA1 pyramidal cells than in thalamus and in hippocampal interneurons. In behavioral tests, ampakines facilitate learning in many paradigms including odor discrimination, spatial mazes, and conditioning, and they improved short-term memory in a non-matching-to-sample task. Positive results were also obtained in various psychological tests with human subjects. The drugs were effective in correcting behaviors in various animal models of schizophrenia and depression. Lastly, evidence is discussed that ampakines have few adverse effects at therapeutically relevant concentrations and that they protect neurons against neurotoxic insults, in part by mobilizing growth factors like BDNF. Type II drugs like CX516 in particular appear to be inherently safe since their ability to prolong responses is kinetically limited.

Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior. Publishing Authors By Initials

AC Arai,M Kessler,

For similar nervous system: synapses research abstracts see: nervous system: synapses research

PUBMED ID PMID:

MEDLINE DATE:

Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior. Journal Published:

PUBLICATION TYPE: Review

Journal: Current drug targets

VOLUME: 8

Page Numbers: 583-602

Journal Abbreviation:

ISSN: 1873-5592

DAY: 3

MONTH: May

YEAR: 2007

Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior. Information

Number of References: 190

LANGUAGE: eng

NlmUniqueID: 100960531

Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior. Keywords Mesh Terms:

KEYWORDS: Synapses

MESH TERMS: physiology

Chemical & Substance for Abstract: Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior. Information

Substance Name: aniracetam

Registry Number: 72432-10-1

Grant and Affiliation Information for Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior.

AFFILIATION: Dept of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9629, USA. aarai@siumed.edu

Country: Netherlands

AGENCY: United States NINDS

GRANT: NS41020

ACRONYM: NS

MEDLINETA: Curr Drug Targets

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior Related Publications

• About the suboccipital part of the vertebral artery and the neighboring bone-joint and nerve relationships.
• Arthritis and physical-mental comorbidity in metropolitan China.
• Broadening the definition of generalized anxiety disorder: effects on prevalence and associations with other disorders in the National Comorbidity Survey Replication.
• Changes in surgical therapy for Crohn's disease over 33 years: a prospective longitudinal study.
• Clinical differences among patients treated for mental health problems in general medical and specialty mental health settings in the National Comorbidity Survey Replication.
• Complete robotic-assistance during laparoscopic living donor nephrectomies: an evaluation of 38 procedures at a single site.
• Concordance of the Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) with standardized clinical assessments in the WHO World Mental Health surveys.
• DSM-IV personality disorders in the National Comorbidity Survey Replication.
• Delay in initial treatment contact after first onset of mental disorders in metropolitan China.
• Developmental changes in progenitor cell responsiveness to bone morphogenetic proteins differentially modulate progressive CNS lineage fate.
• Developmental changes in progenitor cell responsiveness to cytokines.
• Dual function of Sox1 in telencephalic progenitor cells.
• FoxD3 and Grg4 physically interact to repress transcription and induce mesoderm in Xenopus.
• FoxD3 regulation of Nodal in the Spemann organizer is essential for Xenopus dorsal mesoderm development.
• Lifetime prevalence and inter-cohort variation in DSM-IV disorders in metropolitan China.
• Lifetime prevalence, correlates, and persistence of oppositional defiant disorder: results from the National Comorbidity Survey Replication.
• Mental disorders among English-speaking Mexican immigrants to the US compared to a national sample of Mexicans.
• Mental health service use among hurricane Katrina survivors in the eight months after the disaster.
• Multiple congenital coagulopathies co-expressed with Von Willebrand's disease: the experience of Hemophilia Region III Treatment Centers over 25 years and review of the literature.
• Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior.
• Postcircumcision necrosis of the glans penis: gray-scale and color Doppler sonographic findings.
• Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators.
• Psychiatric epidemiology: challenges and opportunities.
• Risk for psychiatric disorder among immigrants and their US-born descendants: evidence from the National Comorbidity Survey Replication.
• Sonic hedgehog and BMP2 exert opposing actions on proliferation and differentiation of embryonic neural progenitor cells.
• Telephone screening, outreach, and care management for depressed workers and impact on clinical and work productivity outcomes: a randomized controlled trial.
• The costs and benefits of enhanced depression care to employers.
• The impact of comorbidity of mental and physical conditions on role disability in the US adult household population.
• The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication.
• Understanding mental health treatment in persons without mental diagnoses: results from the National Comorbidity Survey Replication.