363 results match your criteria procognitive effects

Erythropoietin and Non-Erythropoietic Derivatives in Cognition.

Front Pharmacol 2021 6;12:728725. Epub 2021 Sep 6.

Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States.

Cognitive deficits are widespread in psychiatric disorders, including major depression and schizophrenia. These deficits are known to contribute significantly to the accompanying functional impairment. Progress in the development of targeted treatments of cognitive deficits has been limited and there exists a major unmet need to develop more efficacious treatments. Read More

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September 2021

Structure-Based Design and Optimization of FPPQ, a Dual-Acting 5-HT and 5-HT Receptor Antagonist with Antipsychotic and Procognitive Properties.

J Med Chem 2021 Sep 1;64(18):13279-13298. Epub 2021 Sep 1.

Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Str., 31-343 Kraków, Poland.

In line with recent clinical trials demonstrating that ondansetron, a 5-HT receptor (5-HTR) antagonist, ameliorates cognitive deficits of schizophrenia and the known procognitive effects of 5-HT receptor (5-HTR) antagonists, we applied the hybridization strategy to design dual-acting 5-HT/5-HTR antagonists. We identified the first-in-class compound , which behaves as a 5-HTR antagonist and a neutral antagonist 5-HTR of the Gs pathway. shows selectivity over 87 targets and decent brain penetration. Read More

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September 2021

Improvements of Frontotemporal Cerebral Blood Flow and Cognitive Functioning in Patients With First Episode of Schizophrenia Treated With Long-Acting Aripiprazole.

J Clin Psychopharmacol 2021 Aug 26. Epub 2021 Aug 26.

From the Department of Psychiatry, University Hospital Centre Sestre Milosrdnice School of Medicine, Catholic University of Croatia Department of Oncology and Nuclear Medicine, University Hospital Centre Sestre Milosrdnice, Zagreb, Croatia.

Purpose/background: Frontal and temporal cerebral blood flow (CBF) changes are the most common impairments of CBF described in patients with schizophrenia. Those impairments have also been associated with cognitive deficits, a hallmark of schizophrenia. In light of that fact, treatment interventions should target cognitive deficits to prevent chronic disability. Read More

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Interaction of clozapine with metformin in a schizophrenia rat model.

Sci Rep 2021 Aug 19;11(1):16862. Epub 2021 Aug 19.

Institute of Biochemistry, ELKH Biological Research Center, 6726, Szeged, Hungary.

The low efficacy of antipsychotic drugs (e.g., clozapine) for negative symptoms and cognitive impairment has led to the introduction of adjuvant therapies. Read More

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Effects of a novel M4 muscarinic positive allosteric modulator on behavior and cognitive deficits relevant to Alzheimer's disease and schizophrenia in rhesus monkey.

Neuropharmacology 2021 Oct 11;197:108754. Epub 2021 Aug 11.

Department of Neuroscience Research, Merck & Co., Inc., West Point, PA, USA. Electronic address:

Alzheimer's disease (AD) is a profoundly debilitating neurodegenerative disorder characterized most notably by progressive cognitive decline, but also agitation and behavioral disturbances that are extremely disruptive to patient and caregiver. Current pharmacological treatments for these symptoms have limited efficacy and significant side effects. We have recently reported the discovery of Compound 24, an M4 positive allosteric modulator (PAM) that is potent, highly selective, and devoid of cholinergic-like side effects in rats. Read More

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October 2021

Potentiation of cognitive enhancer effects of Alzheimer's disease medication memantine by alpha7 nicotinic acetylcholine receptor agonist PHA-543613 in the Morris water maze task.

Psychopharmacology (Berl) 2021 Aug 13. Epub 2021 Aug 13.

János Szentágothai Research Center, Center for Neuroscience, University of Pécs, 20 Ifjúság str, 7624, Pécs, Hungary.

Rationale: There are controversial pieces of evidence whether combination therapies using memantine and cholinesterase inhibitors are beneficial over their monotreatments. However, results of preclinical studies are promising when memantine is combined with agonists and allosteric modulators of the alpha7 nicotinic acetylcholine receptor (nAChR).

Objectives: Here, we tested the hypothesis that cognitive enhancer effects of memantine can be potentiated through modulating alpha7 nAChRs in a scopolamine-induced amnesia model. Read More

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-Skatyltryptamines-Dual 5-HTR/DR Ligands with Antipsychotic and Procognitive Potential.

Molecules 2021 Jul 29;26(15). Epub 2021 Jul 29.

Department of Medicinal Chemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland.

A series of -skatyltryptamines was synthesized and their affinities for serotonin and dopamine receptors were determined. Compounds exhibited activity toward 5-HT, 5-HT, 5-HT, and D receptors. Substitution patterns resulting in affinity/activity switches were identified and studied using homology modeling. Read More

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Efficacy and safety of lurasidone in children and adolescents: Recommendations for clinical management and future research.

Curr Pharm Des 2021 Aug 3. Epub 2021 Aug 3.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa. Italy.

Lurasidone is a novel azapirone derivative, and atypical antipsychotic agent with a high binding affinity for dopaminergic (D2), serotoninergic (5-HT2A), and 5-HT7 receptors (antagonist), a moderate affinity for 5-HT1A receptors (partial agonist), and no appreciable affinity for histaminergic (H1) and muscarinic (M1) receptors. It was recently included by the European Medication Agency among the in-label pharmacological treatments for children and adolescents affected by early onset schizophrenia. As a dopamine and serotonin antagonist, lurasidone acts on a variety of receptors and showed its efficacy both as an antipsychotic and an activating compound. Read More

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Lithium: A therapeutic option in Alzheimer's disease and its prodromal stages?

Neurosci Lett 2021 08 10;760:136044. Epub 2021 Jun 10.

Department of Psychiatry, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.

Experimental data reveal that lithium is capable of attenuating Alzheimer's disease pathology and stimulating adult hippocampal neurogenesis. Clinical studies show procognitive effects in lithium-treated patients with amnestic MCI and Alzheimer's disease. These procognitive effects are associated with changes of CSF biomarkers of Alzheimer's disease. Read More

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Some Candidate Drugs for Pharmacotherapy of Alzheimer's Disease.

Pharmaceuticals (Basel) 2021 May 13;14(5). Epub 2021 May 13.

Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland.

Alzheimer's disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The available pharmacological treatment is of a symptomatic nature and, as such, it does not modify the cause of AD. The currently used drugs to enhance cognition include an N-methyl-d-aspartate receptor antagonist (memantine) and cholinesterase inhibitors. Read More

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Apigenin and Structurally Related Flavonoids Allosterically Potentiate the Function of Human α7-Nicotinic Acetylcholine Receptors Expressed in SH-EP1 Cells.

Cells 2021 05 5;10(5). Epub 2021 May 5.

Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Safat 13110, Kuwait.

Phytochemicals, such as monoterpenes, polyphenols, curcuminoids, and flavonoids, are known to have anti-inflammatory, antioxidant, neuroprotective, and procognitive effects. In this study, the effects of several polyhydroxy flavonoids, as derivatives of differently substituted 5,7-dihydroxy-4-chromen-4-one including apigenin, genistein, luteolin, kaempferol, quercetin, gossypetin, and phloretin with different lipophilicities (cLogP), as well as topological polar surface area (TPSA), were tested for induction of Ca transients by α7 human nicotinic acetylcholine (α7 nACh) receptors expressed in SH-EP1 cells. Apigenin (10 μM) caused a significant potentiation of ACh (30 μM)-induced Ca transients, but did not affect Ca transients induced by high K (60 mM) containing solutions. Read More

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Biperiden Challenge Model in Healthy Elderly as Proof-of-Pharmacology Tool: A Randomized, Placebo-Controlled Trial.

J Clin Pharmacol 2021 May 21. Epub 2021 May 21.

Centre for Human Drug Research, Leiden, The Netherlands.

Selective M muscarinic acetylcholine receptor (mAChR) agonists are being developed as symptomatic treatment for neurodegenerative and neuropsychiatric disorders that lead to cognitive dysfunction. Demonstrating cognition-enhancing effects in early-phase clinical development in healthy subjects is difficult. A challenge with the M mAChR antagonist biperiden could be used to demonstrate procognitive and pharmacological effects of selective M mAChR agonists. Read More

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The selective 5-HT receptor biased agonists, F15599 and F13714, show antidepressant-like properties after a single administration in the mouse model of unpredictable chronic mild stress.

Psychopharmacology (Berl) 2021 Aug 10;238(8):2249-2260. Epub 2021 May 10.

Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.

Rationale: The prevalence of depression is ever-increasing throughout the population. However, available treatments are ineffective in around one-third of patients and there is a need for more effective and safer drugs.

Objectives: The antidepressant-like and procognitive effects of the "biased agonists" F15599 (also known as NLX-101) which preferentially targets postsynaptic 5-HT receptors and F13714, which targets 5-HT autoreceptors, were investigated in mice. Read More

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Differential effects of alkaloids on memory in rodents.

Sci Rep 2021 05 10;11(1):9843. Epub 2021 May 10.

PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland.

Nicotinic acetylcholine receptors (nAChRs) play a critical role in the neuropharmacology of learning and memory. As such, naturally occurring alkaloids that regulate nAChR activity have gained interest for understanding and potentially improving memory function. In this study, we tested the acute effects of three known nicotinic alkaloids, nicotine, cotinine, and anatabine, in suppressing scopolamine-induced memory deficit in rodents by using two classic memory paradigms, Y-maze and novel object recognition (NOR) in mice and rats, respectively. Read More

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Prefrontal corticotropin-releasing factor neurons impair sustained attention via distal transmitter release.

Eur J Neurosci 2021 May 5. Epub 2021 May 5.

Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.

The prefrontal cortex (PFC) supports cognitive processes critical for goal-directed behavior. Although the PFC contains a high density of corticotropin-releasing factor (CRF) neurons, their role in cognition has been largely unexplored. We recently demonstrated that CRF neurons in the caudal dorsomedial PFC (dmPFC) of rats act to impair working memory via activation of local CRF receptors. Read More

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Repeated treatment with alpha 7 nicotinic acetylcholine receptor ligands enhances cognitive processes and stimulates Erk1/2 and Arc genes in rats.

Behav Brain Res 2021 Jul 30;409:113338. Epub 2021 Apr 30.

Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Behavioral Neuroscience and Drug Development, Krakow, Poland.

The α7 nicotinic acetylcholine receptor (α7 nAChR) is a potential target for the treatment of cognitive decline in patients with schizophrenia, Alzheimer's disease, and attention-deficit/hyperactivity disorder. Here we examined the promnesic activity of the α7 nAChR agonist (A582941), the type I (CCMI), and the type II (PNU120596) positive allosteric modulators (PAMs) in rats following single and repeated (once daily for seven days) treatment. To determine the neuronal mechanisms underlying the procognitive activity of the tested compounds, levels of the extracellular signal-regulated kinases (Erk1/2) and the activity-regulated cytoskeleton-associated protein (Arc) mRNAs were assessed in the frontal cortical and hippocampal brain regions. Read More

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The Calcium/Calmodulin-Dependent Kinases II and IV as Therapeutic Targets in Neurodegenerative and Neuropsychiatric Disorders.

Int J Mol Sci 2021 Apr 21;22(9). Epub 2021 Apr 21.

Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.

CaMKII and CaMKIV are calcium/calmodulin-dependent kinases playing a rudimentary role in many regulatory processes in the organism. These kinases attract increasing interest due to their involvement primarily in memory and plasticity and various cellular functions. Although CaMKII and CaMKIV are mostly recognized as the important cogs in a memory machine, little is known about their effect on mood and role in neuropsychiatric diseases etiology. Read More

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Short- and Long-Term Social Recognition Memory Are Differentially Modulated by Neuronal Histamine.

Biomolecules 2021 04 9;11(4). Epub 2021 Apr 9.

Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology of Toxicology, University of Florence, 50019 Florence, Italy.

The ability of recognizing familiar conspecifics is essential for many forms of social interaction including reproduction, establishment of dominance hierarchies, and pair bond formation in monogamous species. Many hormones and neurotransmitters have been suggested to play key roles in social discrimination. Here we demonstrate that disruption or potentiation of histaminergic neurotransmission differentially affects short (STM) and long-term (LTM) social recognition memory. Read More

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Biased agonism in drug discovery: Is there a future for biased 5-HT receptor agonists in the treatment of neuropsychiatric diseases?

Pharmacol Ther 2021 Apr 24;227:107872. Epub 2021 Apr 24.

Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland. Electronic address:

Serotonin (5-HT) is one of the fundamental neurotransmitters that contribute to the information essential for an organism's normal, physiological function. Serotonin acts centrally and systemically. The 5-HT receptor is the most widespread serotonin receptor, and participates in many brain-related disorders, including anxiety, depression, and cognitive impairments. Read More

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2-Phenyl-1-pyrrole-3-carboxamide as a New Scaffold for Developing 5-HT Receptor Inverse Agonists with Cognition-Enhancing Activity.

ACS Chem Neurosci 2021 04 11;12(7):1228-1240. Epub 2021 Mar 11.

Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Str., 30-688 Kraków, Poland.

Serotonin type 6 receptor (5-HTR) has gained particular interest as a promising target for treating cognitive deficits, given the positive effects of its antagonists in a wide range of memory impairment paradigms. Herein, we report on degradation of the 1-pyrrolo[3,2-]quinoline scaffold to provide the 2-phenyl-1-pyrrole-3-carboxamide, which is devoid of canonical indole-like skeleton and retains recognition of 5-HTR. This modification has changed the compound's activity at 5-HTR-operated signaling pathways from neutral antagonism to inverse agonism. Read More

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Anti-PTSD Effects of Hypidone Hydrochloride (YL-0919): A Novel Combined Selective 5-HT Reuptake Inhibitor/5-HT Receptor Partial Agonist/5-HT Receptor Full Agonist.

Front Pharmacol 2021 10;12:625547. Epub 2021 Feb 10.

Department of Anesthesiology, the First Medical Center, Chinese PLA General Hospital, Beijing, China.

Posttraumatic stress disorder (PTSD) is a debilitating trauma and stressor-related disorder that has become a major neuropsychiatric problem, leading to substantial disruptions in individual health and societal costs. Our previous studies have demonstrated that hypidone hydrochloride (YL-0919), a novel combined selective 5-HT reuptake inhibitor/5-HT receptor partial agonist/5-HT receptor full agonist, exerts notable antidepressant- and anxiolytic-like as well as procognitive effects. However, whether YL-0919 exerts anti-PTSD effects and its underlying mechanisms are still unclear. Read More

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February 2021

Mechanisms of the Procognitive Effects of Xanthotoxin and Umbelliferone on LPS-Induced Amnesia in Mice.

Int J Mol Sci 2021 Feb 10;22(4). Epub 2021 Feb 10.

Independent Laboratory of Behavioral Studies, Medical University of Lublin, 4A Chodzki Str., 20-093 Lublin, Poland.

Neuroinflammation plays an essential role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. Although coumarins have been shown to improve cognitive function in animal models and exert anti-inflammatory effects in cell cultures, the exact mechanism of their neuroprotective effects has not yet been fully elucidated. The present study aimed to investigate the neuroprotective effects of xanthotoxin (furanocoumarin) and umbelliferone (simple coumarin) in lipopolysaccharide-induced cognitive dysfunction in mice. Read More

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February 2021

Transcranial Direct Current Stimulation to the Left Dorsolateral Prefrontal Cortex Improves Cognitive Control in Patients With Attention-Deficit/Hyperactivity Disorder: A Randomized Behavioral and Neurophysiological Study.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 04 25;6(4):439-448. Epub 2020 Nov 25.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with significant morbidity and mortality that may affect over 5% of children and approximately 2.8% of adults worldwide. Pharmacological and behavioral therapies for ADHD exist, but critical symptoms such as dysexecutive deficits remain unaffected. Read More

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Histamine 3 receptor inverse agonist Samelisant (SUVN-G3031): Pharmacological characterization of an investigational agent for the treatment of cognitive disorders.

J Psychopharmacol 2021 Jun 5;35(6):713-729. Epub 2021 Feb 5.

Suven Life Sciences Ltd, Hyderabad, India.

Background: Central histamine H3 receptors are a family of presynaptic auto and heteroreceptors. Blockade of the presynaptic H3 receptors activates the downstream pathway(s) involved in the processes of learning and memory, making it a potential therapeutic option for ameliorating cognitive dysfunction. Samelisant (SUVN-G3031) is a potent and selective inverse agonist at the H3 receptors. Read More

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Tacrine - Benzothiazoles: Novel class of potential multitarget anti-Alzheimeŕs drugs dealing with cholinergic, amyloid and mitochondrial systems.

Bioorg Chem 2021 02 28;107:104596. Epub 2020 Dec 28.

Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic. Electronic address:

A series of tacrine - benzothiazole hybrids incorporate inhibitors of acetylcholinesterase (AChE), amyloid β (Aβ) aggregation and mitochondrial enzyme ABAD, whose interaction with Aβ leads to mitochondrial dysfunction, into a single molecule. In vitro, several of 25 final compounds exerted excellent anti-AChE properties and interesting capabilities to block Aβ aggregation. The best derivative of the series could be considered 10w that was found to be highly potent and selective towards AChE with the IC value in nanomolar range. Read More

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February 2021

Effect of protocatechuic acid on cognitive processes and central nervous system neuromodulators in the hippocampus, prefrontal cortex, and striatum of healthy rats.

Nutr Neurosci 2020 Dec 21:1-12. Epub 2020 Dec 21.

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Warsaw, Poland.

Objective: : This study aimed to investigate the influence of protocatechuic acid (PCA) on learning, memory, and central nervous system (CNS) neuromodulators in healthy rats, to analyse whether the procognitive effects of PCA found in animal models of memory impairment and described in the literature occur in healthy individuals.

Methods: : PCA was administered for 48 days at doses of 50 or 100 mg/kg body weight. The cognitive performance was analysed in behavioural tests (open field, novel object recognition, water maze). Read More

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December 2020

A Novel Biomarker of Neuronal Glutamate Metabolism in Nonhuman Primates Using Localized H-Magnetic Resonance Spectroscopy: Development and Effects of BNC375, an α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 Sep 29. Epub 2020 Sep 29.

Department of Diagnostic Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut.

Background: The development of treatments for cognitive deficits associated with central nervous system disorders is currently a significant medical need. Despite the great need for such therapeutics, a significant challenge in the drug development process is the paucity of robust biomarkers to assess target modulation and guide clinical decisions. We developed a novel, translatable biomarker of neuronal glutamate metabolism, the C-glutamate+glutamine (Glx) H3:H4 labeling ratio, in nonhuman primates using localized H-magnetic resonance spectroscopy combined with C-glucose infusions. Read More

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September 2020

AMPA receptors mediate the pro-cognitive effects of electrical and optogenetic stimulation of the medial prefrontal cortex in antidepressant non-responsive Wistar-Kyoto rats.

J Psychopharmacol 2020 12 17;34(12):1418-1430. Epub 2020 Nov 17.

Department of Psychology, Swansea University, Swansea, UK.

Background: The chronic mild stress (CMS) procedure is a widely used animal model of depression, and its application in Wistar-Kyoto (WKY) rats has been validated as a model of antidepressant-refractory depression. While not responding to chronic treatment with antidepressant drugs, WKY rats do respond to acute deep brain stimulation (DBS) of the medial prefrontal cortex (mPFC). In antidepressant-responsive strains there is evidence suggesting a role for AMPA subtype of glutamate receptor in the action mechanism of both antidepressants and DBS. Read More

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December 2020

LL-00066471, a novel positive allosteric modulator of α7 nicotinic acetylcholine receptor ameliorates cognitive and sensorimotor gating deficits in animal models: Discovery and preclinical characterization.

Eur J Pharmacol 2021 Jan 27;891:173685. Epub 2020 Oct 27.

Department of Pharmacology, Novel Drug Discovery and Development, Lupin Limited, Lupin Research Park, Pune, Maharashtra, 412115, India.

α7 nicotinic acetylcholine receptor (α7 nAChR) is an extensively validated target for several neurological and psychiatric conditions namely, dementia and schizophrenia, owing to its vital roles in cognition and sensorimotor gating. Positive allosteric modulation (PAM) of α7 nAChR represents an innovative approach to amplify endogenous cholinergic signaling in a temporally restricted manner in learning and memory centers of brain. α7 nAChR PAMs are anticipated to side-step burgeoning issues observed with several clinical-stage orthosteric α7 nAChR agonists, related to selectivity, tolerance/tachyphylaxis, thus providing a novel dimension in therapeutic strategy and pharmacology of α7 nAChR ion-channel. Read More

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January 2021