Deciphering Taste Disorders: Mechanistic Insights and Nonclinical Evaluation

Drug-induced taste dysfunctions are an underrecognized yet clinically significant class of adverse effects that can substantially impair patients' quality of life and compromise adherence to therapeutic regimens. Despite the potential for many pharmacologic agents to alter taste perception, these effects are frequently overlooked in both clinical practice and drug development. Gustatory disorders are rarely assessed in toxicology studies, and current knowledge regarding the pathophysiology of dysgeusia, the relevant organ systems involved, and nonclinical evaluation methods remains limited. This review details the anatomy of the gustatory system including taste buds and papillae, the functional characteristics of taste cells, the molecular mechanisms of taste transduction, and the neural components (peripheral and central). We emphasize the multimodal nature of flavor perception encompassing gustatory, olfactory and somatosensory systems, including the role of saliva in modulating flavor. Furthermore, we propose a comprehensive framework for nonclinical histopathological assessment of the key organ systems involved in flavor perception, with relevant case examples. By advancing awareness and providing optimized approaches for gustatory system evaluation in nonclinical toxicology studies, we aim to enable earlier detection and mechanistic investigation of taste-related adverse effects and improve safety profiling during drug development.