GA0113 is a newly developed angiotensin II (Ang II) AT 1-receptor antagonist having a quinoline moiety. This study was undertaken to clarify the pharmacologic profile of GA0113. In vitro profiles of GA0113 for Ang II receptors were examined in a receptor-binding assay and an Ang II-induced vasoconstriction study. Antihypertensive effects after single or repeated oral administrations were examined in conscious renal hypertensive (RH) or spontaneous hypertensive (SH) rats. Blood pressure (BP) and heart rate were measured by the tail-cuff method. GA0113 interacted with AT 1 receptors in a competitive manner, but showed an insurmountable antagonistic action in Ang II-induced vasoconstriction. In RH rats, GA0113 (0.01-1 mg/kg) reduced BP with ED 25 values of 0.015 mg/kg, and required 0.1 mg/kg for 24-h BP control. Repeated administration of GA0113 in SH rats (0.03-0.1 mg/kg) showed moderate onset and gradually potentiated reduction of BP, which reached a plateau after day 4 of treatment without alteration in heart rate. There was no tolerance of the hypotensive action or rebound phenomenon after cessation of the treatment. In pharmacokinetic studies, GA0113 shows excellent oral bioavailability (94%) and a long circulating half-life (12 h) in rats. These findings indicate that GA0113 may serve as a highly potent and effective antihypertensive agent in humans. GA0113, with its unique chemical structure and pharmacologic and pharmacokinetic profiles may provide new possibilities in hypertension therapy.