TY - JOUR
T1 - Lactamimides
T2 - A novel chemical class of calcium antagonists with diltiazem-like properties
AU - Palfreyman, Michael G.
AU - Dudley, Mark W.
AU - Cheng, Hsien C.
AU - Mir, Anis K.
AU - Yamada, Shizuo
AU - Roeske, William R.
AU - Obata, Takaaki
AU - Yamamura, Henry I.
N1 - Funding Information:
Acknowledgements-The authorws ish to thankA nn-Marie Ogden, E. Martin Gleason, Nelly Edel, ChristianeB erg andM arcelinS ablonef or excellentt echnicala ssistancea nd Mary Dooley andC y Tyson for secretariahl elpi n preparing this manuscriptT. he authorsa re also indebtedt o Drs L. Yuh and E. M. Chi for the derivationo f the equationa nd analysiso f data involved in Table 2. Supportedi n part by U.S.P.H.S. grants.
PY - 1989/8/1
Y1 - 1989/8/1
N2 - The effects of a series of lactamimides on [3H]d-cis-diltiazem binding to rat brain membranes, on [3H]nitrendipine binding to cardiac membranes, and on calcium-induced contractions in depolarized guinea pig taenia and ileum preparations were examined. Several of the lactamimides examined displaced [3H]d-cis-diltiazem binding and antagonized, in a competitive fashion, calcium-induced contractions. Over the series of lactamimides, there was a highly significant, positive linear correlation (r = 0.87, P < 0.001) between their potency to displace [3H]d-cis-diltiazem and their potency to antagonize calcium-induced contractions in the depolarized taenia and ileum preparations. Of the lactamimides examined, MDL 16,582A [N-(2,2-diphenylpentyl)azacyclotridecan-2-imine · hydrochloride] had potency equivalent to d-cis-diltiazem with pA2 values of 7.27 and 7.38, respectively, against calcium-induced contractions in the guinea pig ileum. These lactamimides are a novel chemical class displaying diltiazem-like calcium antagonist properties.
AB - The effects of a series of lactamimides on [3H]d-cis-diltiazem binding to rat brain membranes, on [3H]nitrendipine binding to cardiac membranes, and on calcium-induced contractions in depolarized guinea pig taenia and ileum preparations were examined. Several of the lactamimides examined displaced [3H]d-cis-diltiazem binding and antagonized, in a competitive fashion, calcium-induced contractions. Over the series of lactamimides, there was a highly significant, positive linear correlation (r = 0.87, P < 0.001) between their potency to displace [3H]d-cis-diltiazem and their potency to antagonize calcium-induced contractions in the depolarized taenia and ileum preparations. Of the lactamimides examined, MDL 16,582A [N-(2,2-diphenylpentyl)azacyclotridecan-2-imine · hydrochloride] had potency equivalent to d-cis-diltiazem with pA2 values of 7.27 and 7.38, respectively, against calcium-induced contractions in the guinea pig ileum. These lactamimides are a novel chemical class displaying diltiazem-like calcium antagonist properties.
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U2 - 10.1016/0006-2952(89)90089-0
DO - 10.1016/0006-2952(89)90089-0
M3 - Article
C2 - 2757648
AN - SCOPUS:0024394917
SN - 0006-2952
VL - 38
SP - 2459
EP - 2465
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 15
ER -