| Canine myocardial dihydropyridine binding sites: a positron emission tomographic study with the calcium channel inhibitor 11C-S11568. | |
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MedLine Citation:
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PMID: 7968214 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The in vivo determination of the density of dihydropyridine (DHP) binding sites will allow the assessment of pathophysiological changes associated with heart disease. The calcium channel antagonist S 11568: (+/-)(amino-7 dioxa-2,5 heptyl)-2(dichloro -2,3 phenyl) -4 methyl-6dihydro -1,4 pyridine has an in vitro profile of high potency and of high selectivity for the L-type Ca2+ channel. S 11568 was labelled by a reaction between 11C-diazomethane and the precursor 6-(7-amino-2,5-dioxa heptyl)-4-(2,3-dichloro phenyl)-5-(ethoxycarbonyl)-2 methyl-1,4 dihydro nicotinic acid. (+)-PN 200 110, a DHP with in vitro high affinity for the L-type Ca2+ channel, was also radiolabeled. Positron emission tomographic (PET) studies of both 11C-DHP myocardial uptake were performed in Beagle dogs. 11C-(+)-PN 200 110 had a rapid wash-out from myocardium. In contrary, after a bolus injection, 11C-S 11568 myocardial concentration increased to reach a maximum in 1-2 minutes and then remained in a plateau with a slight downslope while the blood concentration fell rapidly. Myocardial uptake was 2 to 4 fold higher than lung uptake, leading to a good contrast on PET images. Pre-treatment with unlabeled S 11568 (2 mumol/kg or 6 mumol/kg over 15 minutes) reduced myocardial uptake by 60% and 80%, respectively. Specific binding was estimated during a displacement experiment: bolus of unlabeled S 11568: 1 mumol/kg followed by a continuous infusion of 3 mumol/kg over 2 hours. It was found to represent 80% of the total binding. To assess influence of S 11568 on coronary blood flow and therefore on the myocardial tracer delivery, coronary blood flow was measured using 15O-H2O and PET at baseline and following bolus injections of 0.4, 0.8, 2 mumol/kg of S 11568. Only the higher dose increased coronary blood flow. This is the in vivo demonstration of the binding characteristics to myocardial tissue of a DHP ligand. Such properties make S 11568 suitable for PET experiments. The studies of DHP binding sites will provided new insights concerning physiological situations as well as heart disease. |
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Authors:
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H Valette; C Crouzel; A Syrota; C Fuseau; M L Bourachot |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Life sciences Volume: 55 ISSN: 0024-3205 ISO Abbreviation: Life Sci. Publication Date: 1994 |
Date Detail:
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Created Date: 1994-12-01 Completed Date: 1994-12-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1471-7 Citation Subset: IM |
Affiliation:
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Service Hospitalier Frédéric Joliot, DRIPP-CEA, Orsay, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Binding Sites Blood Pressure / drug effects Calcium Channel Blockers / pharmacokinetics*, pharmacology* Carbon Radioisotopes / diagnostic use Coronary Vessels / drug effects, radionuclide imaging Dihydropyridines / metabolism*, pharmacokinetics*, pharmacology* Dogs Female Heart / drug effects, radionuclide imaging* Heart Rate / drug effects Isradipine / pharmacokinetics Myocardium / metabolism*, ultrastructure Tomography, Emission-Computed |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channel Blockers; 0/Carbon Radioisotopes; 0/Dihydropyridines; 132636-01-2/S 11568; 3337-17-5/1,4-dihydropyridine; 75695-93-1/Isradipine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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