The imidazodiazepine, KRM-II-81: An example of a newly emerging generation of GABAkines for neurological and psychiatric disorders

Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies

(2021) Adam Strzelczyk et al.   CNS DRUGS

Balancing the Risks and Benefits of Benzodiazepines

(2021) Matthew E. Hirschtritt et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Intranasal Allopregnanolone Confers Rapid Seizure Protection: Evidence for Direct Nose-to-Brain Delivery

(2021) Dorota Zolkowska et al.   Neurotherapeutics

Safety, Tolerability, and Pharmacokinetics of Multiple Repeated Oral Doses of the α2/3/5‐Subtype Selective GABA A ‐Positive Allosteric Modulator PF‐06372865 in Healthy Volunteers

(2021) Rachel Gurrell et al.   Clinical Pharmacology in Drug Development

Synergistic antihyperalgesic and antinociceptive effects of morphine and methyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate (MP-III-024): a positive allosteric modulator at α2GABAA and α3GABAA receptors

(2021) Mohammad A. Rahman et al.   PSYCHOPHARMACOLOGY

Novel Treatments for Chronic Pain: Moving Beyond Opioids

(2021) Joseph B O'Brien et al.   Translational Research

Comparison of Dental Benzodiazepine Prescriptions From the U.S., England, and Australia From 2013 to 2018

(2021) Leanne Teoh et al.   AMERICAN JOURNAL OF PREVENTIVE MEDICINE

The novel vasopressin receptor (V1aR) antagonist SRX246 reduces anxiety in an experimental model in humans: a randomized proof-of-concept study

(2021) Tiffany R. Lago et al.   PSYCHOPHARMACOLOGY

Biopsychosocial factors and health outcomes associated with cannabis, opioids and benzodiazepines use among older veterans

(2021) Hyojung Kang et al.   AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE

8-Substituted Triazolobenzodiazepines: In Vitro and In Vivo Pharmacology in Relation to Structural Docking at the α1 Subunit-Containing GABAA Receptor

(2021) Lalit K. Golani et al.   Frontiers in Pharmacology

Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia

(2021) Catherine Roch et al.   PSYCHOPHARMACOLOGY

Evaluating the Implementation of a Multicomponent Intervention Consisting of Education and Feedback on Reducing Benzodiazepine Prescriptions by General Practitioners: BENZORED Hybrid Type I Cluster Randomized Controlled Trial

(2021) Isabel Socias et al.   International Journal of Environmental Research and Public Health

Preclinical screening for antidepressant activity – shifting focus away from the Forced Swim Test to the use of translational biomarkers

(2021) Fiona Sewell et al.   REGULATORY TOXICOLOGY AND PHARMACOLOGY

Anti-anxiety Properties of Selected Medicinal Plants

(2021) Asmatullah Khan et al.   CURRENT PHARMACEUTICAL BIOTECHNOLOGY

The Imidazodiazepine Anticonvulsant, KRM-II-81, Produces Novel, Non-diazepam-like Antiseizure Effects

(2020) Daniel E. Knutson et al.   ACS Chemical Neuroscience

An update into the medicinal chemistry of translocator protein (TSPO) ligands

(2020) Elisabetta Barresi et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Shared structural mechanisms of general anaesthetics and benzodiazepines

(2020) Jeong Joo Kim et al.   NATURE

The α2,3-selective potentiators of GABAA receptors, KRM-II-81 and MP-III-80, produce anxiolytic-like effects and block chemotherapy-induced hyperalgesia in mice without tolerance development

(2020) A. Biggerstaff et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Preclinical characterization of zuranolone (SAGE-217), a selective neuroactive steroid GABAA receptor positive allosteric modulator

(2020) Alison L. Althaus et al.   NEUROPHARMACOLOGY

Glutamate Systems in DSM-5 Anxiety Disorders: Their Role and a Review of Glutamate and GABA Psychopharmacology

(2020) Madeeha Nasir et al.   Frontiers in Psychiatry

Understanding the Clinical Effects and Mechanisms of Action of Neurosteroids

(2020) Robert A. Kleinman et al.   AMERICAN JOURNAL OF PSYCHIATRY

Zuranolone as an oral adjunct to treatment of Parkinsonian tremor: A phase 2, open-label study

(2020) Amy Bullock et al.   JOURNAL OF THE NEUROLOGICAL SCIENCES

Brexanolone in Postpartum Depression: Post Hoc Analyses to Help Inform Clinical Decision-Making

(2020) Margaret E. Gerbasi et al.   JOURNAL OF WOMENS HEALTH

Photosensitive epilepsy

(2019) Rachel Gurrell et al.   NEUROLOGY

Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis

(2019) April Slee et al.   LANCET

Extrasynaptic γ‐aminobutyric acid type A receptor–mediated sex differences in the antiseizure activity of neurosteroids in status epilepticus and complex partial seizures

(2019) Doodipala Samba Reddy et al.   EPILEPSIA

Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development

(2019) Ariela Frieder et al.   CNS DRUGS

Effects of the α2/α3-subtype-selective GABAA receptor positive allosteric modulator KRM-II-81 on pain-depressed behavior in rats

(2019) Megan J. Moerke et al.   BEHAVIOURAL PHARMACOLOGY

GABAA receptor subtypes and the abuse-related effects of ethanol in rhesus monkeys: Experiments with selective positive allosteric modulators

(2019) Lais F. Berro et al.   ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH

Potentiating α 2 subunit containing perisomatic GABA A receptors protects against seizures in a mouse model of Dravet syndrome

(2019) Toshihiro Nomura et al.   JOURNAL OF PHYSIOLOGY-LONDON

The α2,3-selective potentiator of GABAA receptors, KRM-II-81, reduces nociceptive-associated behaviors induced by formalin and spinal nerve ligation in rats

(2019) J.M. Witkin et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

SAGE-217, A Novel GABAA Receptor Positive Allosteric Modulator: Clinical Pharmacology and Tolerability in Randomized Phase I Dose-Finding Studies

(2019) Ethan Hoffmann et al.   CLINICAL PHARMACOKINETICS

Brexanolone (Zulresso): Finally, an FDA-Approved Treatment for Postpartum Depression

(2019) Jason G Powell et al.   ANNALS OF PHARMACOTHERAPY

Trial of SAGE-217 in Patients with Major Depressive Disorder

(2019) Handan Gunduz-Bruce et al.   NEW ENGLAND JOURNAL OF MEDICINE

Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders

(2019) Simone B. Sartori et al.   PHARMACOLOGY & THERAPEUTICS

Brexanolone for postpartum depression: A meta-analysis of randomized controlled studies

(2019) Wei Zheng et al.   PSYCHIATRY RESEARCH

Novel investigational therapeutics for generalized anxiety disorder (GAD)

(2019) Bella Schanzer et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

The Positive Allosteric Modulator of α2/3-Containing GABAA Receptors, KRM-II-81, Is Active in Pharmaco-Resistant Models of Epilepsy and Reduces Hyperexcitability after Traumatic Brain Injury

(2019) Jeffrey M. Witkin et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

PCDH19- related Epilepsy Syndrome: A comprehensive Clinical Review

(2019) Debopam Samanta   PEDIATRIC NEUROLOGY

Subtype Selective γ-Aminobutyric Acid Type A Receptor (GABAAR) Modulators Acting at the Benzodiazepine Binding Site: An Update

(2019) Samuele Maramai et al.   JOURNAL OF MEDICINAL CHEMISTRY

Isobolographic Analysis of Antiseizure Activity of the GABA Type A Receptor-Modulating Synthetic Neurosteroids Brexanolone and Ganaxolone with Tiagabine and Midazolam

(2019) Shu-Hui Chuang et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

The pro-psychotic metabotropic glutamate receptor compounds fenobam and AZD9272 share binding sites with monoamine oxidase-B inhibitors in humans

(2019) Katarina Varnäs et al.   NEUROPHARMACOLOGY

Pharmacology in translation: the preclinical and early clinical profile of the novel α2/3 functionally selective GABAA receptor positive allosteric modulator PF-06372865

(2018) Sarah A Nickolls et al.   BRITISH JOURNAL OF PHARMACOLOGY

Bioisosteres of ethyl 8-ethynyl-6-(pyridin-2-yl)-4 H -benzo[ f ]imidazo [1,5- a ][1,4]diazepine-3-carboxylate (HZ-166) as novel alpha 2,3 selective potentiators of GABA A receptors: Improved bioavailability enhances anticonvulsant efficacy

(2018) J.M. Witkin et al.   NEUROPHARMACOLOGY

A randomised, placebo-controlled clinical trial with the α2/3/5 subunit selective GABAA positive allosteric modulator PF-06372865 in patients with chronic low back pain

(2018) Rachel Gurrell et al.   PAIN

An antidepressant-related pharmacological signature for positive allosteric modulators of α2/3-containing GABA A receptors

(2018) K.R. Methuku et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Effect of ganaxolone in patients with posttraumatic stress disorder

(2018) Tomoyuki Kawada   PSYCHOPHARMACOLOGY

An Emerging Circuit Pharmacology of GABA A Receptors

(2018) Elif Engin et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Pronounced antiepileptic activity of the subtype-selective GABAA -positive allosteric modulator PF-06372865 in the GAERS absence epilepsy model

(2018) Venceslas Duveau et al.   CNS Neuroscience & Therapeutics

Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials

(2018) Samantha Meltzer-Brody et al.   LANCET

Allopregnanolone Treatment Improves Plasma Metabolomic Profile Associated with GABA Metabolism in Fragile X-Associated Tremor/Ataxia Syndrome: a Pilot Study

(2018) Eleonora Napoli et al.   MOLECULAR NEUROBIOLOGY

Structure of a human synaptic GABAA receptor

(2018) Shaotong Zhu et al.   NATURE

Improved Synthesis of Anxiolytic, Anticonvulsant, and Antinociceptive α2/α3-GABA(A)-ergic Receptor Subtype Selective Ligands as Promising Agents to Treat Anxiety, Epilepsy, and Neuropathic Pain

(2018) James Cook et al.   SYNTHESIS-STUTTGART

Developmental seizures and mortality result from reducing GABAA receptor α2-subunit interaction with collybistin

(2018) Rochelle M. Hines et al.   Nature Communications

Animal models of depression: pros and cons

(2018) Jaanus Harro   CELL AND TISSUE RESEARCH

Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). II. Drugs in more advanced clinical development

(2018) Meir Bialer et al.   EPILEPSIA

Recurrent epileptiform discharges in the medial entorhinal cortex of kainate-treated rats are differentially sensitive to antiseizure drugs

(2018) Peter J. West et al.   EPILEPSIA

Intravenously Administered Ganaxolone Blocks Diazepam- Resistant Lithium-Pilocarpine-Induced Status Epilepticus in Rats. Comparison with Allopregnanolone.

(2018) Michael S Saporito et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Zinc reduces antiseizure activity of neurosteroids by selective blockade of extrasynaptic GABA-A receptor-mediated tonic inhibition in the hippocampus

(2018) Shu-Hui Chuang et al.   NEUROPHARMACOLOGY

International Union of Basic and Clinical Pharmacology. CVI: GABAA Receptor Subtype- and Function-selective Ligands: Key Issues in Translation to Humans

(2018) Werner Sieghart et al.   PHARMACOLOGICAL REVIEWS

Randomized, double-blind, placebo-controlled phase 2 study of ganaxolone as add-on therapy in adults with uncontrolled partial-onset seizures

(2017) Michael R. Sperling et al.   EPILEPSIA

Neuroactive Steroids. 2. 3α-Hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1′-yl)-19-nor-5β-pregnan-20-one (SAGE-217): A Clinical Next Generation Neuroactive Steroid Positive Allosteric Modulator of the (γ-Aminobutyric Acid)A Receptor

(2017) Gabriel Martinez Botella et al.   JOURNAL OF MEDICINAL CHEMISTRY

A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome

(2017) Andrew Ligsay et al.   Journal of Neurodevelopmental Disorders

Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial

(2017) Stephen Kanes et al.   LANCET

Effects of the synthetic neurosteroid ganaxolone on seizure activity and behavioral deficits in an Angelman syndrome mouse model

(2017) Stephanie L. Ciarlone et al.   NEUROPHARMACOLOGY

Allopregnanolone decreases interictal spiking and fast ripples in an animal model of mesial temporal lobe epilepsy

(2017) Maxime Lévesque et al.   NEUROPHARMACOLOGY

Neonatal bladder inflammation induces long-term visceral pain and altered responses of spinal neurons in adult rats

(2017) Pradeep Kannampalli et al.   NEUROSCIENCE

Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated Tremor/Ataxia Syndrome

(2017) J. Y. Wang et al.   Neurotherapeutics

Further evaluation of the potential anxiolytic activity of imidazo[1,5- a ][1,4]diazepin agents selective for α2/3-containing GABA A receptors

(2017) J.M. Witkin et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Abuse-related effects of subtype-selective GABAA receptor positive allosteric modulators in an assay of intracranial self-stimulation in rats

(2017) Kathryn L. Schwienteck et al.   PSYCHOPHARMACOLOGY

Don’t stress about CRF: assessing the translational failures of CRF1antagonists

(2017) Samantha R. Spierling et al.   PSYCHOPHARMACOLOGY

Social Isolation in Early versus Late Adolescent Mice Is Associated with Persistent Behavioral Deficits That Can Be Improved by Neurosteroid-Based Treatment

(2017) Andrea Locci et al.   Frontiers in Cellular Neuroscience

Ganaxolone: A New Treatment for Neonatal Seizures

(2017) Tamara Yawno et al.   Frontiers in Cellular Neuroscience

First-in-man allopregnanolone use in super-refractory status epilepticus

(2017) Henrikas Vaitkevicius et al.   Annals of Clinical and Translational Neurology

Vortioxetine Treatment for Anxiety Disorder: A Meta-Analysis Study

(2017) Anne Yee et al.   CURRENT DRUG TARGETS

Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats

(2017) Sarawut Lapmanee et al.   PLoS One

Self-administration of progesterone and synthetic neuroactive steroids by male rhesus monkeys

(2016) Zhiqiang Meng et al.   DRUG AND ALCOHOL DEPENDENCE

Synthesis and Characterization of a Novel γ-Aminobutyric Acid Type A (GABAA) Receptor Ligand That Combines Outstanding Metabolic Stability, Pharmacokinetics, and Anxiolytic Efficacy

(2016) Michael M. Poe et al.   JOURNAL OF MEDICINAL CHEMISTRY

Functional Synaptic Integration of Forebrain GABAergic Precursors into the Adult Spinal Cord

(2016) Alex Etlin et al.   JOURNAL OF NEUROSCIENCE

Failed trials for central nervous system disorders do not necessarily invalidate preclinical models and drug targets

(2016) Anton Bespalov et al.   NATURE REVIEWS DRUG DISCOVERY

Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice

(2016) Xingjie Ping et al.   PLoS One

GABAA receptor occupancy by subtype selective GABAAα2,3 modulators: PET studies in humans

(2016) Aurelija Jucaite et al.   PSYCHOPHARMACOLOGY

Benzodiazepine and neuroactive steroid combinations in rats: anxiolytic-like and discriminative stimulus effects

(2016) Barak W. Gunter et al.   PSYCHOPHARMACOLOGY

Traumatic brain injuries

(2016) Kaj Blennow et al.   Nature Reviews Disease Primers

Commentary: Obstacles to the Discovery of Medicines for Psychiatric Disorders in Modern Times§

(2015) Jeffrey Witkin   CNS & Neurological Disorders-Drug Targets

Glutamate and GABA Imbalance Following Traumatic Brain Injury

(2015) Réjean M. Guerriero et al.   Current Neurology and Neuroscience Reports

Emerging drugs for the treatment of anxiety

(2015) James W Murrough et al.   EXPERT OPINION ON EMERGING DRUGS

NS11821, a partial subtype-selective GABAA agonist, elicits selective effects on the central nervous system in randomized controlled trial with healthy subjects

(2015) Rob GJA Zuiker et al.   JOURNAL OF PSYCHOPHARMACOLOGY

Enhancing neurosteroid synthesis – Relationship to the pharmacology of translocator protein (18 kDa) (TSPO) ligands and benzodiazepines

(2015) L Wolf et al.   PHARMACOPSYCHIATRY

The Non-Benzodiazepine Anxiolytic Drug Etifoxine Causes a Rapid, Receptor-Independent Stimulation of Neurosteroid Biosynthesis

(2015) Jean Luc do Rego et al.   PLoS One

Evaluation of the neuroactive steroid ganaxolone on social and repetitive behaviors in the BTBR mouse model of autism

(2015) Tatiana M. Kazdoba et al.   PSYCHOPHARMACOLOGY

The central nervous system effects of the partial GABA-Aα2,3-selective receptor modulator AZD7325 in comparison with lorazepam in healthy males

(2014) Xia Chen et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Off-Label Prescribing of Antiepileptic Drugs in Pharmacoresistant Epilepsy: A Cross-Sectional Drug Utilization Study of Tertiary Care Centers in Italy

(2014) Valentina Franco et al.   CNS DRUGS

Help luck along to find psychiatric medicines

(2014) David Nutt   NATURE

Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework

(2014) David Cook et al.   NATURE REVIEWS DRUG DISCOVERY

Rapid loss of efficacy to the antiseizure drugs lamotrigine and carbamazepine: A novel experimental model of pharmacoresistant epilepsy

(2013) Ajay K. Srivastava et al.   EPILEPSIA

Issues related to development of new antiseizure treatments

(2013) Karen S. Wilcox et al.   EPILEPSIA

Glutamate-based anxiolytic ligands in clinical trials

(2013) Joanna M Wierońska et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Innovative Drugs to Treat Depression: Did Animal Models Fail to Be Predictive or Did Clinical Trials Fail to Detect Effects?

(2013) Catherine Belzung   NEUROPSYCHOPHARMACOLOGY

The Vasopressin V1bReceptor Antagonist SSR149415 in the Treatment of Major Depressive and Generalized Anxiety Disorders

(2012) Guy Griebel et al.   JOURNAL OF CLINICAL PSYCHIATRY

Anxioselective anxiolytics: on a quest for the Holy Grail

(2012) Phil Skolnick   TRENDS IN PHARMACOLOGICAL SCIENCES

Development of Post-Traumatic Epilepsy after Controlled Cortical Impact and Lateral Fluid-Percussion-Induced Brain Injury in the Mouse

(2011) Tamuna Bolkvadze et al.   JOURNAL OF NEUROTRAUMA

The effects of TPA023, a GABAAα2,3 subtype-selective partial agonist, on essential tremor in comparison to alcohol

(2011) SL de Haas et al.   JOURNAL OF PSYCHOPHARMACOLOGY

Neurosteroids as endogenous regulators of seizure susceptibility and use in the treatment of epilepsy

(2010) Doodipala S. Reddy et al.   EPILEPSIA

Comparative anticonvulsant efficacy in the corneal kindled mouse model of partial epilepsy: Correlation with other seizure and epilepsy models

(2010) Nicole M. Rowley et al.   EPILEPSY RESEARCH

Anxiolytic-like effects of 8-acetylene imidazobenzodiazepines in a rhesus monkey conflict procedure

(2010) Bradford D. Fischer et al.   NEUROPHARMACOLOGY

HZ166, a novel GABAA receptor subtype-selective benzodiazepine site ligand, is antihyperalgesic in mouse models of inflammatory and neuropathic pain

(2010) Alessandra Di Lio et al.   NEUROPHARMACOLOGY

Anxiolytic-like effects of the neurokinin 1 receptor antagonist GR-205171 in the elevated plus maze and contextual fear-potentiated startle model of anxiety in gerbils

(2009) Scott A. Heldt et al.   BEHAVIOURAL PHARMACOLOGY

A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study of Efficacy and Safety of Ocinaplon (DOV 273,547) in Generalized Anxiety Disorder

(2009) Pál Czobor et al.   CNS Neuroscience & Therapeutics

A population-based study of risk of epilepsy after hospitalization for traumatic brain injury

(2009) Pamela L. Ferguson et al.   EPILEPSIA

Antiseizure Activity of Novel γ-Aminobutyric Acid (A) Receptor Subtype-Selective Benzodiazepine Analogues in Mice and Rat Models

(2009) Felix M. Rivas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Benzodiazepine Binding Site Occupancy by the Novel GABAA Receptor Subtype-Selective Drug 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine (TPA023) in Rats, Primates, and Humans

(2009) J. R. Atack et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Reducing Abuse Liability of GABAA/Benzodiazepine Ligands via Selective Partial Agonist Efficacy at  1 and  2/3 Subtypes

(2009) N. A. Ator et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

A comparison of the effects of a subtype selective and non-selective benzodiazepine receptor agonist in two CO2 models of experimental human anxiety

(2008) JE Bailey et al.   JOURNAL OF PSYCHOPHARMACOLOGY

Novel discriminative stimulus effects of TPA023B, subtype-selective γ-aminobutyric-acidA/benzodiazepine modulator: Comparisons with zolpidem, lorazepam, and TPA023

(2008) Stephen J. Kohut et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

The microinjection of AMPA receptor antagonist into the accumbens shell, but not into the accumbens core, induces anxiolysis in an animal model of anxiety

(2007) Isabel Cristina da Cunha et al.   BEHAVIOURAL BRAIN RESEARCH