Cirazoline is an α1-adrenergic receptor (α1-AR) agonist (Kis = 120, 960, and 660 nM for recombinant α1A-, α1B-, and α1D-ARs, respectively, in CHO cell membranes). It acts as a full agonist at α1A- and a partial agonist at α1B- and α1D-ARs in vitro (EC50s = 70.7, 79.4, and 239.8 nM, respectively). It also acts as an antagonist at α2-ARs with a pA2 value of 7.56 to inhibit the norepinephrine-induced twitch response in isolated pig ileum. Cirazoline (0.01-1 μg/kg) decreases blood pressure when administered via microinjection to the nucleus reticularis lateralis (NRL) of anesthetized normotensive cats. It enhances spatial memory and reduces depressive- and anxiety-like behavior in mice when administered at a concentration of 10 mg/L in drinking water for 2-9 months. It also enhances performance in the variable delayed response task in aged rhesus monkeys at high doses of 1-10 μg/kg but impairs performance at lower doses of 0.01-1 μg/kg.
