Timothy B. C. Johnstone's research works | University of California, Irvine, CA (UCI) and other places

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Allosteric modulators of the δ GABAA receptor subtype demonstrate a therapeutic effect in morphine-antinociceptive tolerance and withdrawal in mice

Article

Sep 2022

The present study evaluated the effects of compounds targeting extrasynaptic δ subunit-containing γ-aminobutyric acid type A receptors (δ*-GABAARs) to interrogate the role of tonic inhibition in the development of antinociceptive tolerance caused by repeated morphine administration. We investigated the effect of subchronic or acute treatment with n...

FIGURE 1 | Effect of treatment by 2-261 alone or combined with MDZ...

FIGURE 2 | Effect of treatment by 2-261 alone (A) or combined with MDZ...

FIGURE 4 | Effect of treatment by 2-261 alone (A) or combined with MDZ...

Mandatory counting region of interest sizes.

Enaminone Modulators of Extrasynaptic α4β3δ γ-Aminobutyric AcidA Receptors Reverse Electrographic Status Epilepticus in the Rat After Acute Organophosphorus Poisoning

Article

Full-text available

May 2019

Seizures induced by organophosphorus nerve agent exposure become refractory to treatment with benzodiazepines because these drugs engage synaptic γ-aminobutyric acid-A receptors (GABAARs) that rapidly internalize during status epilepticus (SE). Extrasynaptic GABAARs, such as those containing α4β3δ subunits, are a putative pharmacological target to...

Positive Allosteric Modulators of Non-Benzodiazepine γ-Aminobutyric acida Receptor Subtypes for the Treatment of Chronic Pain

Article

Sep 2018

Chronic neuropathic pain may be caused, in part, by loss of inhibition in spinal pain processing pathways due to attenuation of local GABAergic tone. Nociception and nocifensive behaviors are reduced after enhancement of tonically activated extrasynaptic GABAAR mediated currents by agonist ligands for δ subunit-containing GABAARs. However, typical...