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Kubo, K. et al.

Extremely long-acting antihypertensive effects of KF-4317, a alpha- and beta 1-adrenoceptor blocker.

The hypotensive effects of 4-(2-hydroxy-3-[(1-methyl-3-phenylpropyl)amino]propoxy)benzeneacetamide hydrochloride (KF-4317, a novel alpha- and beta 1-adrenoceptor blocker) were evaluated in spontaneously hypertensive rats and renal hypertensive dogs as well as in normotensive dogs, cats and rabbits, using various routes of administration. Single oral, intraduodenal and intravenous administrations of KF-4317 induced definite hypotensive effects. When intraduodenally given to anesthetized rabbits, KF-4317 elicited a much more prolonged effect on the blood pressure than labetalol, while neither atenolol nor propranolol showed hypotensive effects. Pretreatment with phentolamine abolished its depressor effect, but not its bradycardic effect, indicating that the former effect is mediated by alpha-blockade. When orally given to the conscious hypertensive rats and dogs, it exerted an extremely long-acting effect with a property of very gradual onset of action. Furthermore, KF-4317 neither showed any sign indicative of orthostatic hypotension in an experimental model nor exhibited any intrinsic sympathomimetic activity, though a very weak local anesthetic effect was observed. From these results, it could be concluded that KF-4317 possesses some pharmacological properties similar to labetalol, but in contrast to labetalol it is beta 1-selective, and it may be useful in the treatment of patients with hypertension.[1]

References

Extremely long-acting antihypertensive effects of KF-4317, a alpha- and beta 1-adrenoceptor blocker. Kubo, K., Ikeda, J., Nakamura, J., Nakamizo, N. Archives internationales de pharmacodynamie et de thérapie. (1985) [Pubmed]

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