PHARMACOLOGICAL STUDIES OF IMIDAZOLINE DERIVATIVES. III. ACTIONS ON CARDIOVASCULAR SYSTEM AND ACUTE TOXICITY

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The effects of 8 imidazoline derivatives on the cardiovascular system and their acute toxicity were investigated. In anesthetized rats, K-6341 and K-6343 produced relatively long-lasting elevation of blood pressure. This hypertensive response was prevented by prazosin. In contrast, K-4011,K-3827 and K-4300 exerted long-lasting hypotensive actions. Norepinephrine-induced increase in blood pressure was competitively antagonized by these three derivatives. Therefore, the hypertensive and hypotensive actions of imidazoline derivatives are conceivably exerted by activating and blocking α_1-adrenoceptors. In the isolated guinea-pig atrial preparations, K-4011,K-3827,K-6341 and K-6343 produced positive inotropic responses which were independent of β-adrenoceptor activation. The positive inotropic effect of K-6341,which was the most potent, was specifically attenuated or abolished by diltiazem, suggesting that a change in Ca^<2+> movement across the cell membrane is contributing to K-6341-induced increase in atrial contractions. The main symptoms of mice manifested when injected with imidazoline derivatives were a decrease in spontaneous movement, exophthalmos, an increase in palpebral opening, paralysis of four limbs and respiratory depression. Acute LD_<50> values of imidazoline derivatives in mice (i.v., i.p.) were between these of tolazoline and naphazoline.
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