Document Detail

Canine myocardial dihydropyridine binding sites: a positron emission tomographic study with the calcium channel inhibitor 11C-S11568.
MedLine Citation:
PMID:  7968214     Owner:  NLM     Status:  MEDLINE    
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.
H Valette; C Crouzel; A Syrota; C Fuseau; M L Bourachot
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Life sciences     Volume:  55     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  1994  
Date Detail:
Created Date:  1994-12-01     Completed Date:  1994-12-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1471-7     Citation Subset:  IM    
Service Hospitalier Frédéric Joliot, DRIPP-CEA, Orsay, France.
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MeSH Terms
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*
Heart / drug effects,  radionuclide imaging*
Heart Rate / drug effects
Isradipine / pharmacokinetics
Myocardium / metabolism*,  ultrastructure
Tomography, Emission-Computed
Reg. No./Substance:
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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