Effects of dihydropyridine derivatives and anticonvulsant drugs on [3H]nitrendipine binding and calcium and sodium fluxes in brain.
The binding of [3H]nitrendipine to rat cortical membranes was reduced by phenytoin, phenobarbital, and pentobarbital. The IC50 values were 0.09, 0.40, and 0.76 mM respectively. The drugs reduced the apparent binding affinity of [3H]nitrendipine with little effect on the maximum number of binding sites. The inhibitory effects of the drugs were similar in the absence and presence of calcium (4.5 mM). Neither nimodipine (10(-8) to 10(-5) M) nor nifedipine (10(-8) to 10(-7) M) altered the voltage-dependent uptake of 45Ca2+ by synaptosomes from rat cortex. Phenytoin inhibited 45Ca2+ influx, and this inhibition was not altered by nifedipine. Nimodipine and nifedipine (10(-6) M) produced a small inhibition of the voltage-dependent uptake of 24Na+ by synaptosomes. Ethanol, phenytoin or pentobarbital reduced 24Na+ influx, and this action was not altered by nimodipine. Thus, sedative-anticonvulsant drugs reduced the binding of dihydropyridines to brain membranes, but these interactions did not appear to involve either calcium or sodium channels.
Harris
R A
RA
Jones
S B
SB
Bruno
P
P
Bylund
D B
DB
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001463:Barbiturates / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism; D009568:Nitrendipine; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D014316:Tritium
D000927:Anticonvulsants; D001463:Barbiturates; D014316:Tritium; D000431:Ethanol; D010672:Phenytoin; D009568:Nitrendipine; D012964:Sodium; D009543:Nifedipine; D002118:Calcium