Isoguvacine (hydrochloride)

Isoguvacine is a GABA_A receptor agonist.¹ It binds to rat synaptic cortical membranes (K_i = 55 nM) and activates α₁β₂γ_2S, α₂β₂γ_2S, α₃β₂γ_2S, α₅β₂γ_2S, and ρ₁ subunit-contanining GABA_A receptors in a FLIPR assay (EC₅₀s = 13, 4.5, 5.6, 0.78, and 3.1 µM, respectively).¹ It inhibits CA1 population spikes in rat hippocampal slices (EC₅₀ = 13 µM) and high potassium/low magnesium-induced seizures in rat pups.^2,3 Chronic administration of isoguvacine (2 mg/kg) improves tactile over-reactivity, anxiety-like behaviors, and social impairments in mouse models of autism spectrum disorder (ASD).⁴

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1. Petersen, J.G., Sørensen, T., Damgaard, M., et al. Synthesis and pharmacological evaluation of 6-aminonicotinic acid analogues as novel GABA_A receptor agonists. Eur. J. Med. Chem. 84, 404-416 (2014).

2. Kemp, J.A., Marshall, G.R., and Woodruff, G.N. Quantitative evaluation of the potencies of GABA-receptor agonists and antagonists using the rat hippocampal slice preparation. Br. J. Pharmacol. 87(4), 677-684 (1986).

3. Isaev, D., Isaeva, E., Khazipov, R., et al. Anticonvulsant action of GABA in the high potassium-low magnesium model of ictogenesis in the neonatal rat hippocampus in vivo and in vitro. J. Neurophysiol. 94(4), 2987-2992 (2005).

4. Orefice, L.L., Mosko, J.R., Morency, D.T., et al. Targeting peripheral somatosensory neurons to improve tactile-related phenotypes in ASD models. Cell 178(4), 867-886 (2019).