Interactions of analogs of the 1,4-dihydropyridine tiamdipine in cardiac and smooth muscle.
Two series of 1,4-dihydropyridines related to tiamdipine, 2-(2-aminoethylthio)methyl-3-carboethoxy-5-carbomethoxy-6- methyl-4-(3-nitrophenyl)-1,4-dihydropyridine, have been evaluated for their pharmacologic and radioligand binding properties in smooth and cardiac muscle. In the tiamdipine series the influence of phenyl ring substitution, 3-Cl, 3-MeO and 3-CF3, was greatly reduced relative to the N-formyl and neutral nifedipine derivatives. Consistent with our previous observations onset and offset of action were greatly reduced by the presence of the amine side chain. In tiamdipine analogs also bearing an asymmetric substituent at C-2, chirality at C-4 was determinant for activity.
Galletti
F
F
Department of Biochemical Pharmacology, School of Pharmacy, State University, New York, Buffalo 14260.
Zheng
W
W
Gopalakrishnan
M
M
Rutledge
A
A
Triggle
D J
DJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C066605:tiamdipine