Pharmacokinetic investigation of TRPA1 receptor antagonists: A967079 and HC-030031 in mouse model

Our investigation aimed to delineate the pharmacokinetic parameters of the most commonly used TRPA1 receptor antagonists, A967079 and HC-030031, concerning their drug-likeness and penetration into the central nervous system (CNS). Both substances were tested at two different dosages and two different formulations using the intraperitoneal and subcutaneous routes of administration. We determined the drug-like properties of the substances using several different models. Our findings demonstrate that both substances are able to pass the blood-brain barrier and remain in the CNS for a relatively long period when administered via the appropriate mode and formulation. In the case of A967079, effective concentrations can not only be achieved but also maintained for hours in both plasma and brain tissue. In the case of HC-030031, a shorter residence time and less favourable kinetics are observed. During the study, elimination half-lives were determined separately for plasma and brain tissue, and the brain-to-plasma distribution ratio was calculated. In addition to elimination kinetics, the temporal distribution of the compounds in the liver and kidney was also assessed. Overall, these results provide important pharmacokinetic insights that may facilitate further investigation of TRPA1 ion channel inhibition as a potential therapeutic strategy.