Koch P, Schneider J, Fruh C, Wilhelm D, Wilffert B, Peters T
Janssen Research Foundation, Neuss, F.R.G.
Arch Int Pharmacodyn Ther. 1989 May-Jun;299:134-43.
In pithed normotensive rats, the benzothiazolamine derivative R 56865 in high doses exhibits a competitive antagonism of alpha 1-adrenoceptor-mediated vasoconstrictions. The absence of a depression of the maximum of the dose-response curve of ST 587 and the very moderate attenuation of the maximal B-HT 920-induced increase in diastolic blood pressure (BP) confirms the lack of major calcium entry blocking properties of R 56865 for alpha-adrenoceptor-activated calcium channels in vitro. In doses up to 10(-5) mol/kg, the interaction of R 56865 with the sympathetic neurotransmission can solely be explained by alpha 1-adrenoceptor blockade. This was confirmed by the comparable antagonism of the selective alpha 1-adrenoceptor antagonist prazosin in a concentration of 6 x 10(-8) mol/kg. In contrast to the isolated rat aorta, where R 56865 showed an allosteric interaction with the NA binding site on the alpha 1-adrenoceptor, R 56865 acts like an alpha 1-adrenoceptor antagonist of the competitive type in vivo.
在脊髓横断的正常血压大鼠中，高剂量的苯并噻唑胺衍生物R 56865对α1-肾上腺素能受体介导的血管收缩表现出竞争性拮抗作用。ST 587剂量-反应曲线的最大值未降低，且B-HT 920诱导的舒张压（BP）最大升高非常适度地减弱，这证实了R 56865在体外对α-肾上腺素能受体激活的钙通道缺乏主要的钙内流阻断特性。在高达10^(-5) mol/kg的剂量下，R 56865与交感神经传递的相互作用仅可通过α1-肾上腺素能受体阻断来解释。这在浓度为6×10^(-8) mol/kg的选择性α1-肾上腺素能受体拮抗剂哌唑嗪的类似拮抗作用中得到了证实。与离体大鼠主动脉不同，在离体大鼠主动脉中R 56865与α1-肾上腺素能受体上的去甲肾上腺素（NA）结合位点表现出变构相互作用，而在体内R 56865表现为竞争性类型的α1-肾上腺素能受体拮抗剂。
