Hosohata Y, Hattori K, Shen Y, Okuyama M, Kaneko H, Ohnuki T, Suzuki J, Nagatomo T
Department of Pharmacology, Niigata College of Pharmacy, Niigata, Japan.
Pharmacology. 1998 Oct;57(4):180-7. doi: 10.1159/000028240.
The dissociating and/or residual inhibitory effects of bopindolol from beta-adrenoceptors of atria strips pretreated with this drug which was then washed out with buffers on the responses to isoprenaline were determined and compared with those of propranolol, pindolol, atenolol, and the two active metabolites of bopindolol: 18-502 and 20-785. Low concentrations of bopindolol (10(-9) to 10(-8) mol/l) and the active metabolite 18-502 (10(-9) mol/l) produced rightward shifts of the concentration-response curves. On the other hand, high concentrations of bopindolol (10(-7) mol/l) and metabolite 18-502 (10(-8) and 10(-7) mol/l) produced a reduced maximum response by isoprenaline, suggesting that these nonparallel rightward shifts have pD2 values of 7.57 (bopindolol) and 7.67 (18-502), respectively, at 0 min after washout with buffers. Pindolol (10(-7) mol/l) and propranolol (10(-7) and 10(-8) mol/l) also produced a rightward shift of isoprenaline response curves, and these concentration-response curves in guinea pig atria strips pretreated with pindolol (10(-7) mol/l) and propranolol (10(-6) mol/l) recovered to control levels. Neither of these drugs, however, reduced the maximum response by isoprenaline. A high concentration (10(-5) mol/l) of atenolol was required for a rightward shift of the isoprenaline concentration-response curve, and this drug also did not reduce the maximum response. Thus, we conclude that bopindolol and metabolite 18-502 slowly dissociate and act as noncompetitive beta-antagonists rather than easily reversible beta-adrenoceptor antagonists.
测定了在用缓冲液冲洗后，波吲洛尔对心房肌条β - 肾上腺素能受体的解离和/或残留抑制作用，并与普萘洛尔、吲哚洛尔、阿替洛尔以及波吲洛尔的两种活性代谢产物18 - 502和20 - 785进行比较。低浓度的波吲洛尔（10⁻⁹至10⁻⁸mol/L）和活性代谢产物18 - 502（10⁻⁹mol/L）使浓度 - 反应曲线右移。另一方面，高浓度的波吲洛尔（10⁻⁷mol/L）和代谢产物18 - 502（10⁻⁸和10⁻⁷mol/L）使异丙肾上腺素的最大反应降低，这表明在用缓冲液冲洗0分钟后，这些非平行右移的pD2值分别为7.57（波吲洛尔）和7.67（18 - 502）。吲哚洛尔（10⁻⁷mol/L）和普萘洛尔（10⁻⁷和10⁻⁸mol/L）也使异丙肾上腺素反应曲线右移，在用吲哚洛尔（10⁻⁷mol/L）和普萘洛尔（10⁻⁶mol/L）预处理的豚鼠心房肌条中，这些浓度 - 反应曲线恢复到对照水平。然而，这些药物均未降低异丙肾上腺素的最大反应。高浓度（10⁻⁵mol/L）的阿替洛尔才能使异丙肾上腺素浓度 - 反应曲线右移，且该药物也未降低最大反应。因此，我们得出结论，波吲洛尔和代谢产物18 - 502解离缓慢，起非竞争性β - 拮抗剂作用，而非易逆性β - 肾上腺素能受体拮抗剂。
