In a phase 1 trial to determine the safety of topical kynurenic acid; Pouches containing 0.00% (placebo), 0.15%, 0.25%, 0.4% and 0.5% of kynurenic acid cream is applied to an occlusive, transparent dressing and applied to a test area on the back of volunteers once for 24 hours to test acute dosing, and once every 24 hours for 30 days to test chronic dosing.

Primary cultures of cells dissociated from the hippocampi or cerebral cortex of 16- to 19-d-old rat fetuses were plated onto collagen-coated 35 mm Petri dishes and 25 cm flasks respectively. Electrophysiological experiments were performed on hippocampal neurons cultured for 7–40 d, and binding assays were performed in 7-d-old primary cultures of the cerebral cortex. Transmembrane macroscopic currents were recorded according to the whole-cell mode of the patch-clamp technique. The composition of the external solution used to bathe the cultured neurons was (in mM): NaCl 165, KCl 5, CaCl2 · 2H2O 1, HEPES 5, dextrose 10 (pH was adjusted to 7.3 with NaOH; osmolarity ∼340 mOsm). The internal solution for recordings from cultured neurons had the following composition (in mm): CsCl 80, CsF 80, EGTA 10, CsOH 22.5, and HEPES 10 (pH was adjusted to 7.3 with CsOH; osmolarity ∼340 mOsm). In the presence of atropine (1 μm) and TTX (200 nm), application of ACh (1 mm) to ∼80% of the cultured hippocampal neurons evoked whole-cell currents that had the characteristics of responses mediated by α7 nAChRs. The amplitudes of ACh (1 mm)-evoked currents were reduced after perfusion of cultured hippocampal neurons by ~ 20 % with an external solution containing KYNA (0.1 μm to 1 mm). The inhibitory effect of KYNA on α7 nAChRs was concentration dependent. It was determined that KYNA blocks α7 nAChRs with an IC50 of 7.1 ± 0.9 μm and an nH of 0.34 ± 0.02.