TY - JOUR
T1 - Ferulidilol
T2 - A vasodilatory and antioxidant adrenoceptor and calcium entry blocker, with ancillary β2-agonist activity
AU - Huang, Yeun Chih
AU - Yeh, Jwu Lai
AU - Wu, Bin Nan
AU - Lo, Yi Ching
AU - Liang, Jhy Chong
AU - Lin, Young Tso
AU - Sheu, Sheng Hsiung
AU - Chen, Ing Jun
PY - 1999
Y1 - 1999
N2 - Intravenous injection of ferulidilol (0.5, 1.0, 1.5 mg kg-1) produced dose-dependent hypotensive and bradycardia responses in pentobarbital- anesthetized Wistar rats. Ferulidilol competitively antagonized (- )isoprenaline-induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses on isolated guinea pig tissues. The parallel shift to the right of the concentration-response curve of (- )isoprenaline suggested that ferulidilol was a β-adrenoceptor antagonist. The apparent pA2 values were 8.04 ± 0.09 for the right atria, 8.03 ± 0.15 for the left atria, and 7.51 ± 0.06 for the trachea, respectively. Ferulidilol was more potent than labetalol. In thoracic aorta experiments, ferulidilol also produced a competitive antagonism of norepinephrine- and CaCl2-induced contraction with pA2 and pKCa-1 values of 7.05 ± 0.03 and 6.04 ± 0.05, respectively. Ferulidilol produced cumulative relaxation responses on isolated tracheal strips from reserpine-treated guinea pigs. The effects were competitively antagonized by ICl 118,551 (10-8-10-6 M), a relatively selective β2-adrenoceptor antagonist. The results implied that ferulidilol had partial β2-agonist activity. In the radioligand binding assay, ferulidilol produced dose-dependent inhibition of [3H]CGP-12177 binding to rat ventricle and lung membranes with K(i) values of 3.40 and 17.94 nM, respectively. In addition, ferulidilol also antagonized [3H]prazosin and [3H]nitrendipine binding to rat brain membrane with K(i) values of 32.48 and 305.01 nM, respectively. These results further confirmed the α/β and calcium entry blocking activities of ferulidilol described in functional studies. Furthermore, ferulidilol (10-8-10-5 M] inhibited lipid peroxidation induced by Fe2+ and ascorbic acid, indicating that it possesses the antioxidant activity inherent in ferulic acid. Our results demonstrate that ferulidilol is a new generation α/β-adrenoceptor blocker with ancillary calcium entry blockade, partial β2-agonist activities and additional antioxidant effects.
AB - Intravenous injection of ferulidilol (0.5, 1.0, 1.5 mg kg-1) produced dose-dependent hypotensive and bradycardia responses in pentobarbital- anesthetized Wistar rats. Ferulidilol competitively antagonized (- )isoprenaline-induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses on isolated guinea pig tissues. The parallel shift to the right of the concentration-response curve of (- )isoprenaline suggested that ferulidilol was a β-adrenoceptor antagonist. The apparent pA2 values were 8.04 ± 0.09 for the right atria, 8.03 ± 0.15 for the left atria, and 7.51 ± 0.06 for the trachea, respectively. Ferulidilol was more potent than labetalol. In thoracic aorta experiments, ferulidilol also produced a competitive antagonism of norepinephrine- and CaCl2-induced contraction with pA2 and pKCa-1 values of 7.05 ± 0.03 and 6.04 ± 0.05, respectively. Ferulidilol produced cumulative relaxation responses on isolated tracheal strips from reserpine-treated guinea pigs. The effects were competitively antagonized by ICl 118,551 (10-8-10-6 M), a relatively selective β2-adrenoceptor antagonist. The results implied that ferulidilol had partial β2-agonist activity. In the radioligand binding assay, ferulidilol produced dose-dependent inhibition of [3H]CGP-12177 binding to rat ventricle and lung membranes with K(i) values of 3.40 and 17.94 nM, respectively. In addition, ferulidilol also antagonized [3H]prazosin and [3H]nitrendipine binding to rat brain membrane with K(i) values of 32.48 and 305.01 nM, respectively. These results further confirmed the α/β and calcium entry blocking activities of ferulidilol described in functional studies. Furthermore, ferulidilol (10-8-10-5 M] inhibited lipid peroxidation induced by Fe2+ and ascorbic acid, indicating that it possesses the antioxidant activity inherent in ferulic acid. Our results demonstrate that ferulidilol is a new generation α/β-adrenoceptor blocker with ancillary calcium entry blockade, partial β2-agonist activities and additional antioxidant effects.
KW - Antioxidant activity
KW - Ferulic acid
KW - Partial β-agonist activity
KW - α/β-adrenoceptor blockade
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U2 - 10.1002/(SICI)1098-2299(199906)47:2<77::AID-DDR3>3.0.CO;2-Q
DO - 10.1002/(SICI)1098-2299(199906)47:2<77::AID-DDR3>3.0.CO;2-Q
M3 - Article
AN - SCOPUS:0032778015
SN - 0272-4391
VL - 47
SP - 77
EP - 89
JO - Drug Development Research
JF - Drug Development Research
IS - 2
ER -