大鼠尾动脉中血管加压素受体介导收缩的新型拮抗剂。

New antagonists of the vasopressin receptor mediated contraction in rat tail artery.

作者信息

Petrusewicz J, Damasiewicz B, Kaliszan R, Juzwa W, Lammek B, Derdowska I

机构信息

Department of Biopharmaceutics and Pharmacodynamics, University of Gdansk, Poland.

出版信息

Pharmacol Res. 1992 Feb-Mar;25(2):167-72. doi: 10.1016/1043-6618(92)91384-s.

DOI:10.1016/1043-6618(92)91384-s

PMID:1386154

Abstract

A perfused isolated rat tail artery preparation was employed to study antagonistic properties of four newly synthesized arginine-vasopressin (AVP) analogues against the V1 receptor. The activity of the agents SCATyr(Me)AVP, OCATyr(Me)AVP, OCAAVP and SCAAVP was related to that of a recognized antagonist d(CH2)5Tyr(Me)AVP. SCATyr(Me)AVP elicited outstanding antagonistic properties by blocking at concentration of 10(-7) M nearly completely the constrictory activity of AVP. At concentration of 10(-9) M the agent inhibited the AVP-induced constriction of artery about 40 times more effectively than the oxytocin (OXT)-induced constriction. The results obtained prove the validity of the structure-activity relationship based search for new potent V1 receptor antagonists.

摘要

采用灌注离体大鼠尾动脉标本，研究四种新合成的精氨酸加压素（AVP）类似物对V1受体的拮抗特性。SCATyr(Me)AVP、OCATyr(Me)AVP、OCAAVP和SCAAVP这几种药物的活性与公认的拮抗剂d(CH2)5Tyr(Me)AVP的活性相关。SCATyr(Me)AVP在10^(-7) M浓度时通过几乎完全阻断AVP的收缩活性而表现出显著的拮抗特性。在10^(-9) M浓度时，该药物抑制AVP诱导的动脉收缩比抑制催产素（OXT）诱导的收缩有效约40倍。所得结果证明了基于构效关系寻找新型强效V1受体拮抗剂的有效性。