Eugenolol: An eugenol-derived β-adrenoceptor blocker with partial β2-agonist and calcium mobilization inhibition associated vasorelaxant activities
✍ Scribed by Sheue-Jiun Chen; Yeun-Chih Huang; Bin-Nan Wu; Ing-Jun Chen
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 226 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0272-4391
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✦ Synopsis
The β-adrenoceptor blocking, vasorelaxant and hypotensive activities of eugenolol (1-(isopropylamino)-3-[(4-allyl-2-methoxy-)phenoxy]-2-propanol) were investigated under in vivo and in vitro conditions. In pentobarbital anesthetized rats, eugenolol (0.1, 0.5, 1.0 mg/kg, i.v.) produced a dose-dependent hypotensive and bradycardia response. Eugenolol also inhibited the tachycardia effects induced by (-)isoproterenol, but did not block arterial pressor responses induced by phenylephrine. In isolated guinea pig tissues, eugenolol competitively antagonized the (-)isoproterenol-induced positive inotropic and chronotropic effects and tracheal relaxation responses. The apparent pA 2 values for eugenolol on right atria, left atria and trachea were 8.23 ± 0.04, 8.36 ± 0.13 and 8.18 ± 0.12, respectively. On tracheal strips of reserpinized guinea pig, cumulative doses of eugenolol (10 -10 -10 -7 M) produced dose-dependent relaxant responses. Preincubating the preparation with ICI 118,551 (10 -8 , 10 -7 , 10 -6 M) shifted the eugenolol concentration-relaxation curve significantly to a region of higher concentrations. Binding characteristics of eugenolol and propranolol were evaluated in [ 3 H]dihydroalprenolol binding to pig ventricular membranes. The Ki values of eugenolol and propranolol were 18.1 ± 3.2 and 3.8 ± 0.5 nM, respectively. In guinea pig isolated thoracic aorta, eugenolol relaxed more potently the contractions induced by phenylephrine than those by high K + . The vasorelaxant effect of eugenolol on phenylephrine-or high K + -induced contraction was not attenuated by TEA or Bay K 8644 pretreatment. Furthermore, eugenolol pretreatment had a greater inhibitory effect on phenylephrine induced phasic contraction than on tonic contraction. These results indicate that eugenolol exhibits non-selective β-blocking and vasorelaxant activity by inhibiting Ca 2+ channels, receptor-mediated Ca 2+ mobilization and by its partial β 2 -agonist activity.