The Discovery of Novel α_2a Adrenergic Receptor Agonists Only Coupling to Gαi/O Proteins by Virtual Screening.

ABSTRACT: Most α₂-AR agonists derived from dexmedetomidine have few structural differences between them and have no selectivity for α_2A/2B-AR or Gi/Gs, which can lead to side effects in drugs. To obtain novel and potent α_2A-AR agonists, we performed virtual screening for human α_2A-AR and α_2B-AR to find α_2A-AR agonists with higher selectivity. Compound P300-2342 and its three analogs significantly decreased the locomotor activity of mice (p < 0.05). Furthermore, P300-2342 and its three analogs inhibited the binding of [³H] Rauwolscine with IC₅₀ values of 7.72 ± 0.76 and 12.23 ± 0.11 μM, respectively, to α_2A-AR and α_2B-AR. In α_2A-AR-HEK293 cells, P300-2342 decreased forskolin

SUBMITTER: Zhou P 

PROVIDER: S-EPMC11241340 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature