GABAkines–Advances in the discovery, development, and commercialization of positive allosteric modulators of GABAA receptors

A Lippa, MM Poe, JL Smith, X Jin, X Ping… - Pharmacology & …, 2022 - Elsevier
Positive allosteric modulators of γ-aminobutyric acid-A (GABA A) receptors or GABAkines
have been widely used medicines for over 70 years for anxiety, epilepsy, sleep, and other …

New GABA-targeting therapies for the treatment of seizures and epilepsy: II. Treatments in clinical development

E Perucca, HS White, M Bialer - CNS drugs, 2023 - Springer
The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the
modulation of neuronal excitability, and a disruption of GABAergic transmission contributes …

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

JM Witkin, A Lippa, JL Smith, X Jin, X Ping… - Pharmacology …, 2022 - Elsevier
GABAkines, or positive allosteric modulators of γ-aminobutyric acid-A (GABA A) receptors,
are used for the treatment of anxiety, epilepsy, sleep, and other disorders. The search for …

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

S Maramai, M Benchekroun, SE Ward… - Journal of medicinal …, 2019 - ACS Publications
γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter within the central
nervous system (CNS) with fast, transsynaptic, and modulatory extrasynaptic effects being …

Antinociceptive effects of α2/α3-subtype-selective GABAA receptor positive allosteric modulators KRM-II-81 and NS16085 in male rats: behavioral specificity

LA Lewter, K Woodhouse, VVNPB Tiruveedhula… - The Journal of …, 2024 - Elsevier
Recent studies suggest that among the gamma-aminobutyric acid type A (GABA A) receptor
subtype heterogeneity, α2/α3 subunits of GABA A receptors mediate pain processing …

KCC2 receptor upregulation potentiates antinociceptive effect of GABAAR agonist on remifentanil-induced hyperalgesia

Y Gao, W Zhan, Y Jin, X Chen, J Cai, X Zhou… - Molecular …, 2022 - journals.sagepub.com
GABAergic system disinhibition played an important role in the pathogenesis of remifentanil-
induced hyperalgesia (RIH). K+-Cl--cotransporter-2 (KCC2) has the potential to enhance the …

Therapeutic effects of KRM-II-81, positive allosteric modulator for α2/3 subunit containing GABAA receptors, in a mouse model of Dravet syndrome

S Nakakubo, Y Hiramatsu, T Goto, S Kimura… - Frontiers in …, 2023 - frontiersin.org
Introduction: Dravet syndrome (DS) is an intractable epilepsy syndrome concomitant with
neurodevelopmental disorder that begins in infancy. DS is dominantly caused by mutations …

Rationalizing the binding and α subtype selectivity of synthesized imidazodiazepines and benzodiazepines at GABAA receptors by using molecular docking studies

LK Golani, MY Mian, T Ahmed, KP Pandey… - Bioorganic & Medicinal …, 2022 - Elsevier
The pharmacological actions exerted by benzodiazepines are dependent on the discrete α
protein subunits of the γ-aminobutyric acid type A receptor (GABA AR). Recent …

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 …

A Biggerstaff, B Kivell, JL Smith, MY Mian… - Pharmacology …, 2020 - Elsevier
Opiate analgesics are one of the treatment options for severe chronic pain, including late-
stage cancer, chronic back pain and other disorders. The recent resurgence in opioid …

Synthesis and Pharmacological Evaluation of Novel 2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole Derivatives as Promising Anxiolytic and Analgesic Agents

DV Maltsev, AA Spasov, PM Vassiliev, MO Skripka… - Molecules, 2021 - mdpi.com
A number of novel 2, 3, 4, 5-tetrahydro [1, 3] diazepino [1, 2-a] benzimidazole derivatives 2
were obtained by alkylation mainly in the 1 H-tautomeric form of 2, 3, 4, 5-tetrahydro [1, 3] …