Bronchodilator and Cardiovascular Effects of NKH477, a Novel Water-Soluble Forskolin Derivative, in Guinea Pigs

The bronchodilator and cardiovascular effects of NKH477 (6-(3-dimethylaminopropionyl)forskolin hydrochloride) were evaluated. In anesthetized guinea pigs, i.v. bolus injections of NKH477 (1-100 μg/kg) inhibited the bronchoconstriction induced by inhaled leukotriene D4, increased the heart rate (HR)...

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1995, Vol.68(3), pp.245-253
Main Authors: Iida, Masashi, Fujita, Naomi, Hosono, Makoto, Sukenaga, Yoshikazu
Format: Article
Language:eng ; jpn
Subjects:
Animals
Biological and medical sciences
Blood pressure
Blood Pressure - drug effects
Bronchodilator
Bronchodilator Agents - pharmacology
Colforsin - analogs & derivatives
Colforsin - pharmacology
Dose-Response Relationship, Drug
Guinea Pigs
Heart rate
Heart Rate - drug effects
Injections, Intravenous
Male
Medical sciences
Muscle, Smooth, Vascular - drug effects
NKH477
Pharmacology. Drug treatments
Respiratory system
Time Factors
Vasodilator Agents - pharmacology
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Summary:The bronchodilator and cardiovascular effects of NKH477 (6-(3-dimethylaminopropionyl)forskolin hydrochloride) were evaluated. In anesthetized guinea pigs, i.v. bolus injections of NKH477 (1-100 μg/kg) inhibited the bronchoconstriction induced by inhaled leukotriene D4, increased the heart rate (HR) and decreased the diastolic arterial blood pressure (DBP) in a dose-dependent manner. The bronchodilator effect of NKH477 was 1500 times more potent than that of aminophylline and 17 times less potent than that of isoproterenol. The selectivity of NKH477 for bronchodilation vs an increase in HR was 15 times higher than that of isoproterenol and similar to that of aminophylline; and vs a decrease in DBP, the selectivity was 4 times higher than that of aminophylline and similar to that of isoproterenol. I.v. infusion of NKH477 (0.1-3 μg/kg/min) for 2 hr dose-dependently inhibited the bronchoconstriction induced by i.v. histamine. Isoproterenol (0.1 μg/kg/min, i.v.) enhanced the bronchoconstriction after termination of the infusion, whereas NKH477 did not. In conscious guinea pigs, inhalation of NKH477 (0.1-5 mg/ml) concentration-dependently inhibited the bronchoconstriction induced by inhaled histamine, and a high concentration of NKH477 (35.4 mg/ml) increased the HR. The bronchodilator effect of inhaled NKH477 was 15 times less potent than that of isoproterenol. The selectivity of inhaled NKH477 was similar to that of isoproterenol. These results indicate that NKH477 may be useful as a bronchodilator.
ISSN:0021-5198
1347-3506
DOI:10.1254/jjp.68.245