Comparative study of effects of angiotensin II receptor antagonist, KD3-671, and angiotensin converting enzyme inhibitor, enalaprilat, on cough reflex in guinea pig.
Angiotensin converting enzyme (ACE) inhibitor prevents the inactivation of bradykinin by inhibiting ACE activity, leading to side effects such as dry cough and angioedema. KD3-671 is a novel nonpeptide angiotensin II antagonist which is expected to exhibit persistent hypotensive action without these side effects. In this study, we investigated the relationship between the pharmacokinetics and cough-inducing effect of this drug in guinea-pig, compared with that of an ACE inhibitor, enalaprilat. KD3-671 was not significantly different from the vehicle treatment in the ability to induce coughing, whereas enalaprilat significantly enhanced coughing compared with the vehicle treatment. Thus, as expected from its mechanism of pharmacological action, KD3-671 did not induce coughing. We suggest that the citric acid-induced guinea pig coughing model will be useful in preclinical studies to examine the effect of drug on pulmonary function.
Miyamoto
H
H
Department of Research Laboratories, Kotobuki Pharmaceutical Co., Ltd., Nagano, Japan.
Ito
K
K
Ito
K
K
Wakabayashi
S
S
Suzaka
H
H
Matsuo
H
H
Iga
T
T
Sawada
Y
Y
D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D019343:Citric Acid; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control*; D015773:Enalaprilat / Q000493:pharmacokinetics / Q000494:pharmacology*; D006168:Guinea Pigs; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D013058:Mass Spectrometry; D011485:Protein Binding; D012018:Reflex / Q000187:drug effects*; D013777:Tetrazoles / Q000493:pharmacokinetics / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001798:Blood Proteins; D007093:Imidazoles; C121117:KD3 671; D013777:Tetrazoles; D000804:Angiotensin II; D019343:Citric Acid; D015773:Enalaprilat