Calcium channel agonist and antagonist effects of the stereoisomers of the dihydropyridine 202-791.
The effects of the pure stereoisomers of the novel dihydropyridine 202-791 on voltage sensitive calcium channels in nerve and cardiac muscle were examined. The (-)-isomer blocked depolarization-induced uptake of 45Ca2+ into NG108-15 neuroblastoma X glioma cells, blocked the depolarization-induced release of [3H]-norepinephrine from PC12 cells and reduced the Vmax of the slow response action potential recorded from guinea pig papillary muscle. In contrast, the (+)-isomer enhanced these same processes. In papillary muscle, greater enhancement of the slow responses was observed at lower stimulation frequencies. Thus, the (-) and (+) stereoisomers of 202-791 can be shown to be calcium channel antagonist and agonist respectively.
Kongsamut
S
S
Kamp
T J
TJ
Miller
R J
RJ
Sanguinetti
M C
MC
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D004095:Dihydropyridines; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000187:drug effects*; D007536:Isomerism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007473:Ion Channels; D011725:Pyridines; C045796:SAN 202791; D002118:Calcium