Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aniracetam is a pyrrolidinone-type cognition enhancer that has been clinically used in the treatment of behavioral and psychological symptoms of dementia following stroke and in Alzheimer's disease. New discoveries in the behavioral pharmacology, biochemistry and pharmacokinetics of aniracetam provided new indications for this drug in the treatment of various CNS disorders or disease states. This article reviews these new findings and describes the effects of aniracetam in various rodent models of mental function impairment or cerebral dysfunction. Also, several metabolites of aniracetam have been reported to affect learning and memory in animals. It is, therefore, conceivable that major metabolites of aniracetam contribute to its pharmacological effects. The animal models, used in pharmacological evaluation of aniracetam included models of hypoattention, hypovigilance-arousal, impulsiveness, hyperactivity, fear and anxiety, depression, impaired rapid-eye movement sleep, disturbed temporal regulation, behavioral performance, and bladder hyperactivity. These are models of clinical disorders or symptoms that may include personality disorders, anxiety, depression, posttraumatic stress disorder, attention-deficit/hyperactivity disorder, autism, negative symptoms of schizophrenia, and sleep disorders. At present, there is no convincing evidence that promising effects of aniracetam in the animal models will guarantee its clinical efficacy. It is conceivable, however, that clinical trials will demonstrate beneficial effects of aniracetam in the above listed disease states. New findings regarding the mechanism of action of aniracetam, its central target sites, and its effects on signal transduction are also discussed in this review article.
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PMID:Aniracetam: its novel therapeutic potential in cerebral dysfunctional disorders based on recent pharmacological discoveries. 1207 May 27

Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system and are important potential drug targets for cognitive enhancement and the treatment of schizophrenia. Allosteric modulators of AMPA receptors promote dimerization by binding to a dimer interface and reducing desensitization and deactivation. The pyrrolidine allosteric modulators, piracetam and aniracetam, were among the first of this class of drugs to be discovered. We have determined the structure of the ligand binding domain of the AMPA receptor subtypes GluA2 and GluA3 with piracetam and a corresponding structure of GluA3 with aniracetam. Both drugs bind to GluA2 and GluA3 in a very similar manner, suggesting little subunit specificity. However, the binding sites for piracetam and aniracetam differ considerably. Aniracetam binds to a symmetrical site at the center of the dimer interface. Piracetam binds to multiple sites along the dimer interface with low occupation, one of which is a unique binding site for potential allosteric modulators. This new site may be of importance in the design of new allosteric regulators.
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PMID:Piracetam defines a new binding site for allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. 2016 15