[Affinity of Z-105 to the 1,4-dihydropyridine type calcium channel and several other receptor bindings in the central nervous system].
The affinity of a 1,4-dihydropyridine (DHP) type calcium channel blocker, NZ-105 ((+/-)-2-[benzyl (phenyl) amino] ethyl 1,4-dihydro-2, 6-dimethyl-5- (5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan- 2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxylate hydrochloride ethanol), on the DHP-binding site in the central nervous system and various receptor sites were compared with nicardipine and diltiazem by the use of a receptor binding assay technique. NZ-105 exhibited a displacement effect against [3H]nimodipine in the rat brain DHP-binding site with a potency similar to that of nicardipine. Nicardipine also inhibited the specific binding of several other [3H]-labelled ligands to their receptor such as adrenergic alpha 1, alpha 2, beta, dopamine D1, D2, opioid mu, delta, and kappa-type receptors. Diltiazem also showed a similar inhibitory property. However, NZ-105 showed only weak inhibition against the binding to these receptors. These results suggest that Z-105 has strong affinity to the DHP-binding site in voltage-dependent calcium channels with higher specificity.
Niwa
M
M
Department of Pharmacology, Gifu University School of Medicine, Japan.
Nozaki
M
M
Kobayashi
M
M
Tsurumi
K
K
D000818:Animals; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D004095:Dihydropyridines / Q000493:pharmacokinetics*; D004110:Diltiazem / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D009529:Nicardipine / Q000493:pharmacokinetics; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D014316:Tritium
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D017981:Receptors, Neurotransmitter; D014316:Tritium; C066425:efonidipine; D009529:Nicardipine; D004110:Diltiazem