体外扎米芬净与毒蕈碱受体相互作用的表征

Characterization of the interaction of zamifenacin at muscarinic receptors in vitro.

作者信息

Watson N, Reddy H, Stefanich E, Eglen R M

机构信息

Institute of Pharmacology, Syntex Discovery Research, Palo Alto, CA 94303, USA.

出版信息

Eur J Pharmacol. 1995 Oct 16;285(2):135-42. doi: 10.1016/0014-2999(95)00394-z.

DOI:10.1016/0014-2999(95)00394-z

PMID:8566131

Abstract

The interaction of zamifenacin ((3R)-(+)-diphenylmethoxy-1-(3,4)-methylenedioxyphenethyl)pi peridine) at muscarinic receptor subtypes was studied using radioligand binding and functional techniques, in vitro. In radioligand binding studies, zamifenacin acted as a competitive antagonist, with the following pKi values; rat cerebral cortex (M1) 7.90 +/- 0.08, myocardium (M2) 7.93 +/- 0.13, submaxillary gland (M3) 8.52 +/- 0.04 and rabbit lung (M4) 7.78 +/- 0.04. In functional studies zamifenacin acted as a surmountable antagonist, exhibiting the following apparent affinity values; canine saphenous vein (putative M1) 7.93 +/- 0.09, guinea-pig left atria (M2) 6.60 +/- 0.04, guinea-pig ileum (M3) 9.31 +/- 0.06, guinea-pig oesophageal muscularis mucosae (M3) 8.84 +/- 0.04, guinea-pig trachea (M3) 8.16 +/- 0.04, and guinea-pig urinary bladder (M3) 7.57 +/- 0.15. Therefore, zamifenacin is selective for muscarinic M3 receptors in guinea-pig ileum, oesophageal muscularis mucosae, trachea and bladder over muscarinic M2 receptors in atria. The degree of muscarinic M3/M2 receptor selectivity depends upon the muscarinic M3 receptor preparation studied.

摘要

采用放射性配体结合和功能技术在体外研究了扎非那新（(3R)-(+)-二苯基甲氧基-1-(3,4)-亚甲二氧基苯乙）哌啶）与毒蕈碱受体亚型的相互作用。在放射性配体结合研究中，扎非那新作为竞争性拮抗剂，其pKi值如下：大鼠大脑皮层（M1）7.90±0.08，心肌（M2）7.93±0.13，下颌下腺（M3）8.52±0.04，兔肺（M4）7.78±0.04。在功能研究中，扎非那新作为可克服的拮抗剂，其表观亲和力值如下：犬隐静脉（假定为M1）7.93±0.09，豚鼠左心房（M2）6.60±0.04，豚鼠回肠（M3）9.31±0.06，豚鼠食管肌层黏膜（M3）8.84±0.04，豚鼠气管（M3）8.16±0.04，豚鼠膀胱（M3）7.57±0.15。因此，与心房中的毒蕈碱M2受体相比，扎非那新对豚鼠回肠、食管肌层黏膜、气管和膀胱中的毒蕈碱M3受体具有选择性。毒蕈碱M3/M2受体选择性的程度取决于所研究的毒蕈碱M3受体制剂。