Antiseizure Properties of Histamine H 3 Receptor Antagonists Belonging 3,4-Dihydroquinolin-2(1 H )-Ones.

H3 R is becoming an attractive and promising target for epilepsy treatment as well as the discovery of antiepileptics. In this work, a series of 6-aminoalkoxy-3,4-dihydroquinolin-2(1 H )-ones was prepared to screen their H3 R antagonistic activities and antiseizure effects. The majority of the target compounds displayed a potent H3 R antagonistic activity. Among them, compounds 2a , 2c , 2h , and 4a showed submicromolar H3 R antagonistic activity with an IC50 of 0.52, 0.47, 0.12, and 0.37 μM, respectively. The maximal electroshock seizure (MES) model screened out three compounds ( 2h , 4a , and 4b ) with antiseizure activity. Meanwhile, the pentylenetetrazole (PTZ)-induced seizure test gave a result that no compound can resist the seizures induced by PTZ. Additionally, the anti-MES action of compound 4a fully vanished when it was administrated combined with an H3 R agonist (RAMH). These results showed that the antiseizure role of compound 4a might be achieved by antagonizing the H3 R receptor. The molecular docking of 2h , 4a , and PIT with the H3 R protein predicted their possible binding patterns and gave a presentation that 2h , 4a , and PIT had a similar binding model with H3 R.