Abstract
The α1A-adrenergic receptor (AR) has a higher affinity for several agonists and antagonists compared to α1B or α1D ARs. Mutagenesis studies were used to determine residues potentially responsible for this subtype selectivity. Oxymetazoline has a 50-fold lower affinity for α1D ARs compared to α1A ARs and also displayed a significant loss of affinity for an α1A Leu-290 to Phe mutant. It was concluded that steric interactions between the α1D ARs Phe-360 and the bulky tert-butyl group of oxymetazoline partially accounts for this lower affinity. Thus, the α1A AR binding pocket may more easily accommodate bulk at the para position of the phenyl ring than the α1D AR.