Pharmacological Reviews最新文献

Bitter perception plays a critical role for the detection of potentially harmful substances in food items for most vertebrates. The detection of bitter compounds is facilitated by specialized receptors located in taste buds of the oral cavity. This work focuses on the receptors, including their sensitivities, structure-function relationships, agonists and antagonists. Moreover, the existence of numerous bitter taste receptor variants in the human population and the fact that several of them affect individual bitter tasting profoundly, is discussed as well. The identification of bitter taste receptors in numerous tissues outside the oral cavity and their multiple proposed roles in these tissues is also described briefly. Although this work is mainly focused on human bitter taste receptors, it is imperative to compare human bitter taste with that of other animals to understand which evolutionary forces might have shaped bitter taste receptors and their functions and to distinguish apparent typical human from rather general features. For the readers who are not too familiar with the gustatory system short descriptions of taste anatomy, signal transduction and oral bitter taste receptor expression are included in the beginning of this article. Significance Statement Apart from their role as sensors for potentially harmful substances in the oral cavity, the numerous additional roles of bitter taste receptors in tissues outside the gustatory system have received much attention recently. For the careful assessment of functions inside and outside the taste system a solid knowledge about the specific and general pharmacological features of these receptors and the growing toolbox available for studying them is imperative and provided in this work.

The purpose of this review is to summarize essential biological, pharmaceutical, and clinical aspects in the field of topically applied medicines that may help scientists when trying to develop new topical medicines. After a brief history of topical drug delivery, a review of the structure and function of the skin and routes of drug absorption and their limitations is provided. The most prevalent diseases and current topical treatment approaches are then detailed, the organization of which reflects the key disease categories of autoimmune and inflammatory diseases, microbial infections, skin cancers, and genetic skin diseases. The complexity of topical product development through to large-scale manufacturing along with recommended risk mitigation approaches are then highlighted. As such topical treatments are applied externally, patient preferences along with the challenges they invoke are then described, and finally the future of this field of drug delivery is discussed, with an emphasis on areas that are more likely to yield significant improvements over the topical medicines in current use or would expand the range of medicines and diseases treatable by this route of administration. SIGNIFICANCE STATEMENT: This review of the key aspects of the skin and its associated diseases and current treatments along with the intricacies of topical formulation development should be helpful in making judicious decisions about the development of new or improved topical medicines. These aspects include the choices of the active ingredients, formulations, the target patient population's preferences, limitations, and the future with regard to new skin diseases and topical medicine approaches.