Receptor interactions of imidazolines influence of ionization constant on the diffusion of clonidine and a series of structurally related imidazolidines into and out of the central nervous system

Clonidine and a series of structural analogs with α-adrenergic properties that have been previously characterized were evaluated for their antihypertensive activity following systemic (intravenous) administration to spontaneously hypertensive rats, and for their ability to elevate blood pressure following central (intracisternal) administration to reserpine-pretreated rats. The peripheral pressor activity after intravenous administration in pithed rats was also determined to evaluate possible differences among the compounds in α-adrenergic activity in the peripheral vasculature. Dose-response relationships for the peripheral pressor activities of the compounds indicate that the α-adrenergic activities of these imidazolidines are similar, consistent with our previous observation. A wide range in the potencies of these imidazolidines was observed when their antihypertensive activities were evaluated after systematic (intravenous) administration to spontaneously hypertensive rats. There was an excellent correlation between the antihypertensive activities of these compounds following systemic administration and their ionization constants (r = 0.90, P