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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-3
|
| pubmed:dateCreated |
1997-2-4
|
| pubmed:abstractText |
The vascular selectivity of NB-818 (isopropyl methyl 2-carbamoyloxymethyl-6-methyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine -3, 5-dicarboxylate), a newly synthesized dihydropyridine derivative, was evaluated in in vitro experiments. NB-818 and nifedipine concentration dependently caused a relaxant effect in rabbit femoral arteries precontracted with 60 mM K+, a negative inotropic effect in guinea-pig papillary muscles, and a negative chronotropic effect in guinea-pig right atria. The onset of these inhibitory effects of NB-818 was much slower than that of nifedipine when compared at concentrations producing the same inhibition. The relaxant effect of NB-818 was about 10 times more potent than that of nifedipine, while the negative inotropic effect of NB-818 was about 100 times less potent than that of nifedipine. As a result, NB-818 showed about 300 times higher vascular selectivity than nifedipine. The two drugs exhibited a similar potency for the negative chronotropic effect. In a whole-cell configuration with voltage clamp, the blocking effect of NB-818 on L-type Ca2+ current (ICa) in guinea-pig ventricular cells appeared much more slowly than that of nifedipine and was hardly washed out. The potency of NB-818 to block ICa was markedly enhanced under depolarized conditions (i.e. at a holding potential of -30 mV) compared to that under polarized conditions (i.e. at a holding potential of -70 mV). Such a voltage-dependent blocking action on ICa was less pronounced for nifedipine. These results indicate that NB-818 is a slow-acting Ca2+ channel antagonist with much high vascular selectivity. Its vascular selectivity may be at least in part related to the marked voltage-dependent inhibition of ICa.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Dihydropyridines,
http://linkedlifedata.com/resource/pubmed/chemical/NPK 1886,
http://linkedlifedata.com/resource/pubmed/chemical/Nifedipine
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0014-2999
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
22
|
| pubmed:volume |
301
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
99-106
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8773452-Animals,
pubmed-meshheading:8773452-Blood Vessels,
pubmed-meshheading:8773452-Calcium Channel Blockers,
pubmed-meshheading:8773452-Calcium Channels,
pubmed-meshheading:8773452-Dihydropyridines,
pubmed-meshheading:8773452-Electrophysiology,
pubmed-meshheading:8773452-Female,
pubmed-meshheading:8773452-Femoral Artery,
pubmed-meshheading:8773452-Guinea Pigs,
pubmed-meshheading:8773452-Heart Atria,
pubmed-meshheading:8773452-Heart Rate,
pubmed-meshheading:8773452-Heart Ventricles,
pubmed-meshheading:8773452-Male,
pubmed-meshheading:8773452-Muscle, Smooth, Vascular,
pubmed-meshheading:8773452-Muscle Relaxation,
pubmed-meshheading:8773452-Myocardial Contraction,
pubmed-meshheading:8773452-Nifedipine,
pubmed-meshheading:8773452-Papillary Muscles,
pubmed-meshheading:8773452-Patch-Clamp Techniques,
pubmed-meshheading:8773452-Rabbits
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
In vitro assessment for vascular selectivity of a new dihydropyridine derivative, NB-818.
|
| pubmed:affiliation |
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
|
| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
|