Thiazolidinediones are partially effective bitter blockers.

Autor:	Nguyen H; Monell Chemical Senses Center, Philadelphia, PA, 19104, USA., Lin C; Monell Chemical Senses Center, Philadelphia, PA, 19104, USA., Sasimovich I; Monell Chemical Senses Center, Philadelphia, PA, 19104, USA., Bell K; Monell Chemical Senses Center, Philadelphia, PA, 19104, USA., Huang A; Monell Chemical Senses Center, Philadelphia, PA, 19104, USA., Leszkowicz E; Dept. Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Gdańsk, Poland., Rawson NE; Monell Chemical Senses Center, Philadelphia, PA, 19104, USA., Reed DR; Monell Chemical Senses Center, Philadelphia, PA, 19104, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Aug 10. Date of Electronic Publication: 2023 Aug 10.
DOI:	10.1101/2023.08.08.552460
Abstrakt:	Purpose: The bad bitter taste of some medicines is a barrier to overcoming non-compliance with medication use, especially life-saving drugs given to children and the elderly. Here we evaluated a new class of bitter blockers (thiazolidinediones; TZDs). Methods: In this study, two TZDs were tested, rosiglitazone (ROSI) and a simpler form of TZD, using a high-potency sweetener as a positive control (neohesperidin dihydrochalcone, NHDC). We tested bitter-blocking effects using the bitter drugs tenofovir alafenamide fumarate (TAF), a treatment for HIV and hepatitis B infection, and praziquantel (PRAZ), a treatment for schistosomiasis, by conducting taste testing with two separate taste panels: a general panel (N=97, 20-23 yrs, 82.5% female, all Eastern European) and a genetically informative panel (N=158, including 68 twin pairs, 18-82 yrs, 76% female, 87% European ancestry). Participants rated the bitterness intensity of the solutions on a 100-point generalized visual analog scale. Findings: Participants in both taste panels rated the bitter drugs TAF and PRAZ as less bitter on average when mixed with NHDC than when sampled alone. ROSI partially suppressed the bitterness of TAF and PRAZ, but effectiveness differed between the two panels: bitterness was significantly reduced for PRAZ but not TAF in the general panel and for TAF but not PRAZ in the genetically informative panel. ROSI was a more effective blocker than the other TZD. Implications: These results suggest that TZDs are partially effective bitter blockers, suggesting other TZDs should be designed and tested with more drugs and on diverse populations to define which ones work best with which drugs and for whom. The discovery of bitter receptor blockers can improve compliance with medication use. Competing Interests: Declarations of interest: none
Databáze:	MEDLINE
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