View : 52 Download: 0

Antagonistic effects of novel non-peptide chlorobenzhydryl piperazine compounds on contractile response to bradykinin in the guinea-pig ileum

Title
Antagonistic effects of novel non-peptide chlorobenzhydryl piperazine compounds on contractile response to bradykinin in the guinea-pig ileum
Authors
Yoo L.K.Jai Y.R.Kim H.-J.Hea-Young P.C.
Ewha Authors
박혜영김화정
SCOPUS Author ID
박혜영scopus; 김화정scopus
Issue Date
2005
Journal Title
European Journal of Pharmacology
ISSN
0014-2999JCR Link
Citation
European Journal of Pharmacology vol. 523, no. 41277, pp. 143 - 150
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Two novel compounds, N-phenylacetyl-N′-(4-methoxybenzyl)-N″-1- (4-chlorobenzhydryl)piperazine iminodiacetic acid triamide (compound I) and N-phenylacetyl-N′-(4-methylbenzyl)-N″-1-(4-chlorobenzhydryl) piperazine iminodiacetic acid triamide (compound II), designed and synthesized as novel non-peptide bradykinin B2 receptor antagonists, were studied for their functional activities in isolated guinea-pig ileum smooth muscle. These compounds were compared with the conventional peptide bradykinin B 2 receptor antagonist, icatibant (H-dArg-Arg-Pro-Hyp-Gly-Thi-Ser- dTic-Oic-Arg-OH) for their in vitro functional activities. Compounds I and II showed highly potent, time-dependent insurmountable antagonism against contractile responses to bradykinin (pKB 8.80 and 8.57, respectively) with progressive reduction of maximum effect maintaining the concentration producing half maximal-response unchanged. Otherwise, icatibant, known as a non-competitive antagonist, showed a rightward displacement of cumulative concentration-response curves to bradykinin with decrease of its maximum effect (pKB 8.73). The IC50 values of compounds I and II were 3.56 × 10- 8 and 6.30 × 10- 8 M, respectively, while that of icatibant was 5.02 × 10- 8 M. The profile of action of compounds I and II varied when contact time was prolonged from 5 to 60 min, whereas that of icatibant did not. The inhibitory effects of the newly synthesized compounds and icatibant on the contractile response to bradykinin were differently reverted by washout (icatibant < 100 min, compounds I and II > 100 min). This class of compounds containing the chlorobenzhydryl piperazine moiety is expected to be a novel non-peptide bradykinin B2 receptor antagonists. © 2005 Elsevier B.V. All rights reserved.
DOI
10.1016/j.ejphar.2005.09.010
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE