(S)-(-)-5-Fluorowillardiine (hydrochloride)

(S)-(-)-5-Fluorowillardiine ((5S)-Fluorowillardiine; (S)-5-Fluorowillardiine) hydrochloride is a potent, highly selective non-NMDA ionotropic glutamate receptor (iGluR, AMPA/Kainate receptor) agonist. (S)-(-)-5-Fluorowillardiine hydrochloride activates high-affinity AMPA-preferring receptors (EC₅₀ = 0.70 μM) and low-affinity kainate-preferring receptors (EC₅₀ = 170 μM), thereby inducing biphasic dose-dependent neurotoxicity/excitotoxicity. (S)-(-)-5-Fluorowillardiine hydrochloride is applicable to research related to schizophrenia, temporal lobe epilepsy, and bipolar disorder^[1][2][3]. In Vitro:(S)-(-)-5-Fluorowillardiine (10-100 μM; 24 h) hydrochloride induces > 90% neurotoxicity in primary cultured murine cortical neurones via a biphasic mechanism, with high-affinity component activity at AMPA receptors (EC₅₀ = 0.70 μM) and low-affinity component activity at kainate receptors (EC₅₀ = 170 μM)^[1].
(S)-(-)-5-Fluorowillardiine (200 nM-60 μM) hydrochloride potently activates AMPA/kainate receptors on primary dissociated cultures of mouse embryonic hippocampal neurons with an equilibrium EC₅₀ of 1.47 μM, induces strong desensitization (92.5%), exhibits cross-desensitization with other willardiine derivatives, and produces a prolonged inward tail current following agonist removal^[2].
(S)-(-)-5-Fluorowillardiine (0.1 nM-1 mM; 2 h) hydrochloride binds to mouse GluK5 kainate receptor subunits expressed in Sf9 cell membranes with a K_i of 1.79 μM, and exhibits similar affinity for GluK5 and GluK1 subunits^[3].