A symmetrical 1,4-dihydropyridine with opposite actions on K(+)-induced contractions in guinea-pig ileum.
The effects of 1,4-dihydro-2,6-dimethyl-4-phenyl-pyridine-3,5-dicarboxylic acid dimethyl ester (DHMP) on Ca2(+)-evoked contractions in potassium-depolarized guinea-pig ileum longitudinal muscle were evaluated. DHMP (1-10 nM) potentiated Ca2(+)-evoked contractions; maximum enhancement was seen at 1 nM. A concentration-dependent inhibition of Ca2(+)-induced contractility was observed at higher concentrations. Racemic BAY K 8644 (1 nM - 1 microM), on the other hand, enhanced ileum responses to Ca2+ with a maximum effect at 3 nM. BAY K 8644, but not DHMP, directly elicited concentration-dependent contractions. The results provide further support for the hypothesis that dihydropyridines can act as both Ca2+ agonists and antagonists.
Nova Pharmaceutical Corporation, Baltimore, MD 21224.
P V
PV
Kaplita
D E
DE
Wilkins
T C
TC
Adams
R C
RC
Hanson
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C033707:1,4-dihydro-2,6-dimethyl-4-phenyl-3,5-pyridinecarboxylic acid dimethyl ester; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011188:Potassium; D002118:Calcium