ArticleCNS & neurological disorders drug targets2026
A Novel Polymorphic Form of Sodium Benzoate (Ω-NaBen): Improved Solubility, Stability, Central Nervous System Effects, and Antipsychotic Activities via D-Amino Acid Regulation.
Article in CNS & neurological disorders drug targets, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionSodium benzoate (NaBen), a D-amino acid oxidase inhibitor, has been demonstrated to possess antipsychotic and cognition-enhancing effects in animal models. However, the clinical findings in patients with schizophrenia and dementia are mixed and inconclusive. To further improve its therapeutic potential, a novel crystalline polymorph of NaBen (Ω-NaBen) was developed. This study evaluated the physicochemical properties and central nervous system (CNS) effects of Ω-NaBen.
methodsThe novel crystalline structure of Ω-NaBen was confirmed by thermogravimetric analysis, differential scanning calorimetry, and X-ray powder diffractometry. Water solubility test and stability test were performed to compare its physicochemical properties. The CNS exposure and D-amino acids levels in brain subregions of Ω-NaBen- and non-Ω-NaBen-treated male mice were determined with LC-MS/MS. Therapeutic effects of Ω-NaBen in the MK-801-induced mouse model were assessed by the open field test, novel object recognition test, and three-chamber social test.
resultsOur findings indicated that Ω-NaBen had a unique crystalline structure and showed better aqueous solubility and crystal stability, either with or without clozapine, compared with amorphous NaBen. Ω-NaBen also showed improved CNS exposure and induced higher levels of D-serine or/and D-alanine in the brain. In MK-801-treated mice, Ω-NaBen displayed enhanced effects in alleviating hyperactivity and stronger potency in relieving cognitive impairment. It also improved efficacy in relieving social deficit, a negative symptom model of schizophrenia. DISCUSSION: This study indicates that the crystalline structure critically influences the potency of bioactive compounds and may represent a rational strategy for optimizing pharmaceutical development.
conclusionOur study demonstrated Ω-NaBen's promising potential as a novel CNS therapeutic due to its favorable physicochemical properties, CNS exposure, and neurochemical and behavioral effects.
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