Effects of dihydropyridine calcium channel blocking drugs on rat brain muscarinic and alpha-adrenergic receptors.
Article Details
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Thayer SA, Welcome M, Chhabra A, Fairhurst AS
Effects of dihydropyridine calcium channel blocking drugs on rat brain muscarinic and alpha-adrenergic receptors.
Biochem Pharmacol. 1985 Jan 15;34(2):175-80.
- PubMed ID
- 2981533 [ View in PubMed]
- Abstract
The dihydropyridine (DHP) Ca2+ channel blocking drugs nicardipine, nitrendipine, nimodipine, felodipine, nifedipine and nisoldipine were examined for activity in inhibiting specific (-)-[3H] QNB and [3H]WB4101 binding to the muscarinic and alpha-adrenergic receptors, respectively, of rat brain. Muscarinic receptor binding was affected most by nicardipine, with felodipine having less activity; the other DHP drugs were essentially inactive at 3 X 10(-5) M. The (+)-stereoisomer nicardipine (KI = 4.07 X 10(-7) M) was 27 times more potent than the (-)-isomer in inhibiting [3H]QNB binding, and this inhibition was found to be competitive. This inhibitory effect of nicardipine was not mediated via interaction with the high-affinity DHP binding site assumed to be associated with a Ca2+ channel. (+)-Nicardipine inhibited the binding of [3H]nitrendipine to this DHP binding site of brain, with a K1 of 9.01 X 10(-11) M, and was 10 times more potent than the (-)-isomer. Thus, the muscarinic receptor was 4200 times less sensitive to (+)-nicardipine than was this DHP binding site. Nicardipine was also the most potent DHP drug inhibiting [3H]WB4104 binding to the alpha-adrenergic receptor, although the other drugs were also somewhat active, in the rank order sequence listed above. This effect of nicardipine on the adrenergic receptor was also stereoselective, with (+)-nicardipine (KI = 3.46 X 10(-7) M) being about 3 times more potent than the (-)-isomer, in producing competitive inhibition of radioligand binding. These data suggest that the effects on brain receptors occur as a result of direct, stereospecific effects of DHP drugs on these receptors and are not due to Ca2+ channel blocking activity of these drugs.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Nicardipine Alpha-1A adrenergic receptor Protein Humans UnknownAntagonistDetails Nicardipine Alpha-1B adrenergic receptor Protein Humans UnknownAntagonistDetails Nicardipine Alpha-1D adrenergic receptor Protein Humans UnknownAntagonistDetails Nicardipine Muscarinic acetylcholine receptor M1 Protein Humans UnknownAntagonistDetails Nicardipine Muscarinic acetylcholine receptor M2 Protein Humans UnknownAntagonistDetails Nicardipine Muscarinic acetylcholine receptor M3 Protein Humans UnknownAntagonistDetails Nicardipine Muscarinic acetylcholine receptor M4 Protein Humans UnknownAntagonistDetails Nicardipine Muscarinic acetylcholine receptor M5 Protein Humans UnknownAntagonistDetails