Direct comparison of the effects of first- and second-generation H₁ -receptor blockers on motor functions in mice

Histamine H1 receptor (H1R) antagonists are widely used to treat allergic reactions; however, their effects on the central nervous system can impair motor functions. This study investigated the impact of first-generation (diphenhydramine and d -chlorpheniramine) and second-generation (epinastine, ketotifen, bepotastine, and levocetirizine) H1R antagonists on motor functions in mice using activity wheel, balance beam, inclined screen, and rotarod tests. First-generation H1R antagonists significantly impaired motor functions, with diphenhydramine exerting stronger effects than those of d -chlorpheniramine. Among the second-generation agents, bepotastine and levocetirizine had minimal effects on all motor functions, whereas epinastine and ketotifen suppressed spontaneous movement, similar to first-generation H1R antagonists but had little effects on balance, postural stability, and coordinated movement. These findings provide valuable insights into the differential effects of first- and second-generation H1R antagonists on motor functions. These results highlight the importance of understanding individual profiles of H1R antagonists to minimize adverse effects, ensure patient safety, and improve quality of life.