James M. Cook
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View article: 450. CEREBELLAR α6GABAA RECEPTOR AS A POTENTIAL THERAPEUTIC TARGET FOR RELIEVING CORE SYMPTOMS OF AUTISM: A PRECLINICAL STUDY IN PRENATAL VALPROIC ACID-EXPOSURE RATS
450. CEREBELLAR α6GABAA RECEPTOR AS A POTENTIAL THERAPEUTIC TARGET FOR RELIEVING CORE SYMPTOMS OF AUTISM: A PRECLINICAL STUDY IN PRENATAL VALPROIC ACID-EXPOSURE RATS Open
Background Autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by social impairment and repetitive behaviors, remains an unmet medical need. Cerebellar abnormalities, particularly loss or hypofunction of Purkinje ce…
View article: α6GABAA receptor positive allosteric modulators targeting trigeminal ganglia for preventing and aborting chronic periorbital allodynia and cephalic pain in both sexes: A mechanistic and comparative preclinical study
α6GABAA receptor positive allosteric modulators targeting trigeminal ganglia for preventing and aborting chronic periorbital allodynia and cephalic pain in both sexes: A mechanistic and comparative preclinical study Open
Migraine remains an unmet medical need, even with new calcitonin gene-related peptide (CGRP)-targeting treatments. The α6 subunit (Gabra6)-containing GABAA receptors (α6GABAARs) are abundant in trigeminal ganglia (TG)…
View article: KRM-II-81, a β3-Preferring GABAA Receptor Potentiator, Blocks Handling-Induced Seizures in Theiler’s Murine Encephalomyelitis Virus-Infected Mice
KRM-II-81, a β3-Preferring GABAA Receptor Potentiator, Blocks Handling-Induced Seizures in Theiler’s Murine Encephalomyelitis Virus-Infected Mice Open
Background: The GABAA receptor (GABAAR) potentiator, KRM-II-81, is being developed as a novel antiseizure medication with reduced potential for sedation, tolerance development, and abuse liability. Although KRM-II-81 has been shown to prov…
View article: Parenteral Nanoemulsion for Optimized Delivery of GL-II-73 to the Brain—Comparative In Vitro Blood–Brain Barrier and In Vivo Neuropharmacokinetic Evaluation
Parenteral Nanoemulsion for Optimized Delivery of GL-II-73 to the Brain—Comparative In Vitro Blood–Brain Barrier and In Vivo Neuropharmacokinetic Evaluation Open
Background/Objectives: GL-II-73 is a positive allosteric modulator that is selective for α5GABAA receptors and has physicochemical properties that favor nanocarrier formulations when parenteral delivery to the central nervous system is des…
View article: Intravenous Nanoemulsions Loaded with Phospholipid Complex of a Novel Pyrazoloquinolinone Ligand for Enhanced Brain Delivery
Intravenous Nanoemulsions Loaded with Phospholipid Complex of a Novel Pyrazoloquinolinone Ligand for Enhanced Brain Delivery Open
Background/Objectives: The novel pyrazoloquinolinone ligand CW-02-79 shows a unique profile of selective binding to σ2 receptors, but its poor solubility in both water and lipids makes its research and development a burdensome task. We aim…
View article: α6GABAA RECEPTOR-SELECTIVE POSITIVE ALLOSTERIC MODULATOR AS A POTENTIAL NOVEL THERAPY FOR AUTISM: A PRECLINICAL STUDY IN OFFSPRING OF VALPROIC ACID-TREATED RATS
α6GABAA RECEPTOR-SELECTIVE POSITIVE ALLOSTERIC MODULATOR AS A POTENTIAL NOVEL THERAPY FOR AUTISM: A PRECLINICAL STUDY IN OFFSPRING OF VALPROIC ACID-TREATED RATS Open
Background Autism Spectrum Disorder (ASD) represents a group of developmental disorders characterized by social impairment and repetitive behaviors with the prevalence around 2.7% [1]. ASD treatment remains an unmet medical need. The patho…
View article: Prolonged blockade of NMDA receptors and positive modulation of a5 GABA A receptors: No changes in depressive-like behavior, while the former slightly increased emotional reactivity in unstressed rats
Prolonged blockade of NMDA receptors and positive modulation of a5 GABA A receptors: No changes in depressive-like behavior, while the former slightly increased emotional reactivity in unstressed rats Open
Introduction: Depression is a multifaceted disorder with a limited therapeutic repertoire. A significant breakthrough in depression research has been the discovery of fast-acting antidepressants that target the glutamate/GABA system, namel…
View article: Procognitive and neurotrophic benefits of α5-GABA-A receptor positive allosteric modulation in a β-amyloid deposition mouse model of Alzheimer’s disease pathology
Procognitive and neurotrophic benefits of α5-GABA-A receptor positive allosteric modulation in a β-amyloid deposition mouse model of Alzheimer’s disease pathology Open
Reduced somatostatin (SST) and SST-expressing GABAergic neurons are well-replicated findings in Alzheimer's disease (AD) and are associated with cognitive deficits. SST cells inhibit pyramidal cell dendrites through α5-GABA-A receptors (α5…
View article: GABA(A) Receptor Activation Drives GABARAP–Nix Mediated Autophagy to Radiation-Sensitize Primary and Brain-Metastatic Lung Adenocarcinoma Tumors
GABA(A) Receptor Activation Drives GABARAP–Nix Mediated Autophagy to Radiation-Sensitize Primary and Brain-Metastatic Lung Adenocarcinoma Tumors Open
In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of …
View article: The deuterated pyrazoloquinolinone targeting α6 subunit-containing GABAA receptor as novel candidate for inhibition of trigeminovascular system activation: implication for migraine therapy
The deuterated pyrazoloquinolinone targeting α6 subunit-containing GABAA receptor as novel candidate for inhibition of trigeminovascular system activation: implication for migraine therapy Open
Introduction The α6 subunit-containing GABA A receptors (α6GABA A Rs) are highly expressed in the trigeminal ganglia (TG), the sensory hub of the trigeminovascular system (TGVS). Hypo-GABAergic transmission in the TG was reported to contri…
View article: Development of non-sedating benzodiazepines with <i>in vivo</i> antischistosomal activity
Development of non-sedating benzodiazepines with <i>in vivo</i> antischistosomal activity Open
The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad-spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resi…
View article: Antinociceptive Effects of α2/α3-Subtype-Selective GABAA Receptor Positive Allosteric Modulators KRM-II-81 and NS16085 in Male Rats: Behavioral Specificity
Antinociceptive Effects of α2/α3-Subtype-Selective GABAA Receptor Positive Allosteric Modulators KRM-II-81 and NS16085 in Male Rats: Behavioral Specificity Open
View article: Extrasynaptic Localization Is Essential for α5GABA <sub>A</sub> Receptor Modulation of Dopamine System Function
Extrasynaptic Localization Is Essential for α5GABA <sub>A</sub> Receptor Modulation of Dopamine System Function Open
Dopamine system dysfunction, observed in animal models with psychosis-like symptomatology, can be restored by targeting gamma-aminobutyric acid type A receptors (GABA A Rs) containing the α5, but not α1, subunit in the ventral hippocampus …
View article: Development of non-sedating antischistosomal benzodiazepines
Development of non-sedating antischistosomal benzodiazepines Open
The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resi…
View article: Sigma-2 receptor modulation has no effect on binge eating and anxiety and reduces locomotion in a rat chronic stress model
Sigma-2 receptor modulation has no effect on binge eating and anxiety and reduces locomotion in a rat chronic stress model Open
View article: Dose-, sex- and time-dependent effects of GL-II-73, an α5GABAA receptor-preferring positive allosteric modulator, on amphetamine-induced hyperlocomotion in C57BL/6 mice
Dose-, sex- and time-dependent effects of GL-II-73, an α5GABAA receptor-preferring positive allosteric modulator, on amphetamine-induced hyperlocomotion in C57BL/6 mice Open
View article: KRM–II–81 suppresses epileptifom activity across the neural network of cortical tissue from a patient with pharmacoresistant epilepsy
KRM–II–81 suppresses epileptifom activity across the neural network of cortical tissue from a patient with pharmacoresistant epilepsy Open
A clinical case of a 19-year-old male patient with pharmacoresistant seizures occurring following parieto-occipital tumor-resection at age 6 is described. Seizure surgery work-up included prolonged video EEG monitoring and head CT without …
View article: Improvement of Cognitive Functions And Neurotrophic Effects through by Α5‐GABAA Receptor Positive Allosteric Modulation in Animal Models of Risk for Alzheimer’s Disease
Improvement of Cognitive Functions And Neurotrophic Effects through by Α5‐GABAA Receptor Positive Allosteric Modulation in Animal Models of Risk for Alzheimer’s Disease Open
Background Reduced GABA/somatostatin (SST) signaling is reported in psychiatric, stress‐related and neurodegenerative disorders. SST+ interneurons from cortical layers and the hippocampus inhibit the dendrites of excitatory neurons, largel…
View article: GABA(A) receptor activation drives GABARAP-Nix mediated autophagy to radiation-sensitize primary and brain-metastatic lung adenocarcinoma tumors
GABA(A) receptor activation drives GABARAP-Nix mediated autophagy to radiation-sensitize primary and brain-metastatic lung adenocarcinoma tumors Open
In non-small cell lung cancer (NSCLC) treatment, targeted therapies benefit only a subset of NSCLC, while radiotherapy responses are not durable and toxicity limits therapy. We find that a GABA(A) receptor activator, AM-101, impairs viabil…
View article: Therapeutic effects of KRM-II-81, positive allosteric modulator for α2/3 subunit containing GABAA receptors, in a mouse model of Dravet syndrome
Therapeutic effects of KRM-II-81, positive allosteric modulator for α2/3 subunit containing GABAA receptors, in a mouse model of Dravet syndrome Open
Introduction: Dravet syndrome (DS) is an intractable epilepsy syndrome concomitant with neurodevelopmental disorder that begins in infancy. DS is dominantly caused by mutations in the SCN1A gene, which encodes the α subunit of a voltage-ga…
View article: SEX-DEPENDENT EFFECTS OF A POSITIVE ALLOSTERIC MODULATOR OF GABAA-Α5 RECEPTORS IN AN ANIMAL MODEL FOR AUTISM
SEX-DEPENDENT EFFECTS OF A POSITIVE ALLOSTERIC MODULATOR OF GABAA-Α5 RECEPTORS IN AN ANIMAL MODEL FOR AUTISM Open
View article: Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73
Preformulation and development of preliminary nanoemulsion carrier for patent protected compound GL-II-73 Open
View article: An alpha 5-GABAa receptor positive allosteric modulator attenuates social and cognitive deficits without changing dopamine system hyperactivity in an animal model for autism
An alpha 5-GABAa receptor positive allosteric modulator attenuates social and cognitive deficits without changing dopamine system hyperactivity in an animal model for autism Open
Autism Spectrum Disorders (ASD) are characterized by core behavioral symptoms in the domains of sociability, language/communication, and repetitive or stereotyped behaviors. Deficits in the prefrontal and hippocampal excitatory/inhibitory …
View article: Freeze-dried nanocrystal dispersion of novel deuterated pyrazoloquinolinone ligand (DK-I-56-1): Process parameters and lyoprotectant selection through the stability study
Freeze-dried nanocrystal dispersion of novel deuterated pyrazoloquinolinone ligand (DK-I-56-1): Process parameters and lyoprotectant selection through the stability study Open
View article: α5-GABAA Receptor Modulation Reverses Behavioral and Neurophysiological Correlates of Psychosis in Rats with Ventral Hippocampal Alzheimer’s Disease-like Pathology
α5-GABAA Receptor Modulation Reverses Behavioral and Neurophysiological Correlates of Psychosis in Rats with Ventral Hippocampal Alzheimer’s Disease-like Pathology Open
Of the 35 million people in the world suffering from Alzheimer’s Disease (AD), up to half experience comorbid psychosis. Antipsychotics, used to treat psychosis, are contraindicated in elderly patients because they increase the risk of pre…
View article: GL-II-73, a Positive Allosteric Modulator of α5GABAA Receptors, Reverses Dopamine System Dysfunction Associated with Pilocarpine-Induced Temporal Lobe Epilepsy
GL-II-73, a Positive Allosteric Modulator of α5GABAA Receptors, Reverses Dopamine System Dysfunction Associated with Pilocarpine-Induced Temporal Lobe Epilepsy Open
Although seizures are a hallmark feature of temporal lobe epilepsy (TLE), psychiatric comorbidities, including psychosis, are frequently associated with TLE and contribute to decreased quality of life. Currently, there are no defined thera…
View article: Extrasynaptic localization is essential for α5GABA<sub>A</sub>receptor modulation of dopamine system function
Extrasynaptic localization is essential for α5GABA<sub>A</sub>receptor modulation of dopamine system function Open
Dopamine system dysfunction, observed in animal models with psychosis-like symptomatology, can be restored by targeting Gamma-Aminobutyric Acid type A receptors (GABA A R) containing the α5, but not α1, subunit in the ventral hippocampus (…
View article: Synthesis and Receptor Binding Studies of α5 GABAAR Selective Novel Imidazodiazepines Targeted for Psychiatric and Cognitive Disorders
Synthesis and Receptor Binding Studies of α5 GABAAR Selective Novel Imidazodiazepines Targeted for Psychiatric and Cognitive Disorders Open
GABA mediates inhibitory actions through various GABAA receptor subtypes, including 19 subunits in human GABAAR. Dysregulation of GABAergic neurotransmission is associated with several psychiatric disorders, including depression, anxiety, …
View article: Masthead: (Adv. Electron. Mater. 6/2023)
Masthead: (Adv. Electron. Mater. 6/2023) Open
View article: α5-GABAA receptor modulation reverses behavioral and neurophysiological correlates of psychosis in rats with ventral hippocampal Alzheimer’s Disease-like pathology
α5-GABAA receptor modulation reverses behavioral and neurophysiological correlates of psychosis in rats with ventral hippocampal Alzheimer’s Disease-like pathology Open
Of the 35 million people in the world who suffer with Alzheimer’s Disease (AD), up to half also experience comorbid psychosis (delusions and hallucinations). Antipsychotics, used to treat symptoms of psychosis, are contraindicated in elder…