Lactamimides: a novel chemical class of calcium antagonists with diltiazem-like properties.
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 less than 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.
Palfreyman
M G
MG
Merrell Dow Research Institute, Cincinnati, OH 45215.
Dudley
M W
MW
Cheng
H C
HC
Mir
A K
AK
Yamada
S
S
Roeske
W R
WR
Obata
T
T
Yamamura
H I
HI
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D004110:Diltiazem / Q000378:metabolism; D006168:Guinea Pigs; D007097:Imines / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009568:Nitrendipine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D007097:Imines; D009568:Nitrendipine; D004110:Diltiazem