Wang Tao, Glendinning John, Grushka Miriam, Hummel Thomas, Mansfield Keith
Preclinical Safety, Novartis Institutes for BioMedical Research, Emeryville, California.
Department of Biology, Barnard College, Columbia University, New York, New York.
Toxicol Sci. 2017 Apr 1;156(2):315-324. doi: 10.1093/toxsci/kfw263.
More than 200 medications can induce taste disorders in patients. They not only reduce quality of life for those affected, but can lead to malnutrition, severe dehydration and difficulty in maintaining a therapeutic regimen. Nevertheless, the impact of drug candidates on taste is rarely evaluated in preclinical toxicology studies during the early stage of drug development. Moreover, knowledge about how to investigate these adverse effects is scarce in the toxicology field. Here, we discuss the clinical status of drug-induced taste disorders in patients, with the goal of providing toxicologists with a broad understanding of its prevalence, and how stressful and even dangerous it can be to affected patients. Because taste, smell, and oral trigeminal sensation are highly interdependent, we also address drug-induced changes in olfactory and oral somatosensory perceptions. We then review the biology of the gustatory system (including anatomy and histology), and the latest developments about how taste contributes to flavor perception. Finally, we feature recently optimized preclinical approaches to investigate drug-induced taste change in animal models, including morphological evaluation of taste buds and taste cells, gustatory nerve recording, and behavioral testing. Our goals are to raise awareness of drug-induced taste disorders among toxicologists, share an overview of new approaches and key studies that can be used to identify drug-induced gustatory system toxicity early in the drug development process, and to stimulate further research at this emerging interface of chemosensory disorders with toxicology.
200多种药物可导致患者味觉障碍。这不仅会降低患者的生活质量，还可能导致营养不良、严重脱水以及难以维持治疗方案。然而，在药物研发早期的临床前毒理学研究中，很少评估候选药物对味觉的影响。此外，毒理学领域中关于如何研究这些不良反应的知识也很匮乏。在此，我们讨论药物引起的味觉障碍在患者中的临床状况，目的是让毒理学家广泛了解其患病率，以及它对受影响患者可能造成的压力甚至危险程度。由于味觉、嗅觉和口腔三叉神经感觉高度相互依存，我们还探讨了药物引起的嗅觉和口腔躯体感觉的变化。然后，我们回顾了味觉系统的生物学（包括解剖学和组织学），以及味觉如何影响风味感知的最新进展。最后，我们重点介绍了最近优化的临床前方法，用于研究动物模型中药物引起的味觉变化，包括味蕾和味觉细胞的形态学评估、味觉神经记录和行为测试。我们的目标是提高毒理学家对药物引起的味觉障碍的认识，分享可用于在药物研发过程早期识别药物引起的味觉系统毒性的新方法和关键研究的概述，并激发在化学感觉障碍与毒理学这一新兴交叉领域的进一步研究。
