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C Prenant

Publications and source records attributed to C Prenant.

29 records · Page 2Linked to original sources
PubMed1986

Peripheral-type benzodiazepine receptors in the living heart characterized by positron emission tomography.

The presence of specific benzodiazepine binding sites in the hearts of dogs and human beings was demonstrated in vivo by a noninvasive method, positron emission tomography (PET). An antagonist of the peripheral-type benzodiazepine binding site, PK 11195, was labeled with carbon-11, a short-lived positron emitter. When injected at high specific activity, 11C-PK 11195 was concentrated in the myocardium. As increasing amounts of unlabeled PK 11195 were added to the radioactive ligand, the myocardial ligand concentration was proportional to myocardial regional perfusion up to quantities of 40 nmol/kg body weight. Above 40 nmol/kg the ligand concentration reached a maximum value (6000 pmol/cm3), which could be considered as the total number of binding sites per unit heart volume. The specificity of 11C-PK 11195 binding to canine heart was demonstrated from a study on the inhibition of binding for radioligand by an excess of several agonists or antagonists of benzodiazepine receptor. The distribution and specificity of 11C-PK 11195 was similar in dogs and in human beings. PET thus opens the way to the investigation of the peripheral-type benzodiazepine receptor in a clinical situation, since it has recently been shown that this receptor could be coupled to the calcium channel in the heart.

Animals↗
PubMed1985

Visualization by positron emission tomography of the apparent regional heterogeneity of central type benzodiazepine receptors in the brain of living baboons.

The feasibility of visualizing the heterogeneity of benzodiazepine (BDZ) receptors in the brain of living baboons was investigated using Positron Emission Tomography. Ethyl 8-fluoro-5,6-dihydro-5-methyl 6-oxo-4H-imidazo (1,5-a) (1, 4) benzodiazepine-3-carboxylate (RO 15 1788) labelled by carbon 11 (11C-RO 15 1788) was I.V. injected for the "in vivo" labelling of the central type BDZ receptors. Displacement experiments were performed 20 minutes after the administration of the radioligand by two different cold drugs: RO 15 1788 which has an equal affinity for central type BDZ receptors, and propyl B-Carboline-3-carboxylate (B-CCP) which favours the sites located in the cerebellum. Different sensitivities to these two drugs displacement of 11C-RO 15 1788 binding "in vivo" were observed: on the one hand in the regional localization of the displacement, and on the other hand, in the amount of the radioactivity displaced. The apparent interregional heterogeneity of the displacement seen in the cerebellum and in the temporal cortex are discussed in terms of discrepancies observed "in vitro" at physiological temperature, between cerebellar and non-cerebellar BDZ central type binding sites.

Animals↗
PubMed1984

Central type benzodiazepine binding sites: a positron emission tomography study in the baboon's brain.

An in vivo characterization of specific central type benzodiazepine (BZD) binding sites, labelled with [11C]Ro 15-1788 was performed, using positron emission tomography. After i.v. injection of 10 mCi [11C]Ro 15-1788 (corresponding to 1 nmol/kg), sequential quantitative tomographic slices of the brain were obtained during 80 min. In some experiments various doses of different cold drugs (BZD agonist or antagonist) were injected i.v. subsequently in order to explore the specificity of the binding of the radioligand in brain structures. The main criteria usually utilized in vitro to demonstrate a specific binding to receptors, such as regional distribution, stereospecificity and saturability of the binding and pharmacological effect linked to the receptor's occupancy, were demonstrated in the brain of a living baboon.

Animals↗
PubMed1984

llC labelling of a protein: concanavalin A.

A method is described for the 11C labelling of a phytoagglutinin, concanavalin A, involving reductive methylation by formaldehyde and sodium cyanoborohydride. The reaction mixture is then chromatographed by gel permeation. The quantities (20-80 mCi) and specific activities (20-170 mCi/mg) obtained are such that a practical application of the method is possible. No evidence was found, however, of any preferential uptake of concanavalin A by Krebs II ascite cells in Swiss mice.

Animals↗
PubMed1984

Synthesis of ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo [1,5-a] [1,4]benzodiazepine-3-carboxylate (RO 15.1788-11C): a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography.

A method of labelling ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine-3-carboxylate (RO 15.1788 11C), a benzodiazepine antagonist with carbon-11 has been developed. RO 15.1788-11C was prepared by methylation of the nor derivative by I11CH3. About 100 mCi (maximum 153 mCi, 5.66 GBq) of the chemically and radiochemically pure labelled product were obtained within 25 min with a specific activity on average of 1100 mCi/mumol (maximum 1740 mCi/mu mol--64.4 GBq/mu mol). Preliminary results obtained after i.v. administration in the baboon have shown RO 15.1788-11C to be of interest as a benzodiazepine radioligand for the in vivo study of benzodiazepine receptors by positron emission tomography.

Animals↗
PubMed1983

[11C-Ro15-1788 and 11C-flunitrazepam, two coordinates for the study by positron emission tomography of benzodiazepine binding sites].

In vivo binding of a benzodiazepine (flunitrazepam-C11) and a benzodiazepine antagonist (Ro 15-1788-C11) were studied with positron emission tomography. Advantages and disadvantages of each drug for studying specific in vivo binding sites are presented. The results obtained indicate that Ro 15-1788-C11 is a better in vivo radiocoordinat than flunitrazepam-C11.

Animals↗
PubMed1983

[In vivo study of benzodiazepine receptors using positron emission tomography].

The results obtained by positron-emission tomography in an "in vivo" study on the baboon using a benzodiazepine (flunitrazepam) labeled with carbon-11 are presented. The specificity of "in vivo" binding of Flunitrazepam-11C was demonstrated by competition with Lorazepam in the brain, but it was not possible to verify the criterium of stereospecificity "in vivo". The preliminary results of a study carried out under the same conditions on RO 15 1788 11C show the interest of using this labeled antagonist as an "in vivo" ligand for the specific binding sites of benzodiazepines in positron-emission tomography.

Animals↗
PubMedDate not supplied

Relationships between benzodiazepine receptors, impairment of GABAergic transmission and convulsant activity of beta-CCM: a PET study in the baboon Papio papio.

Central type benzodiazepine receptors were studied in vivo by positron emission tomography in brain areas of 2 different groups of the baboon Papio papio: non-photosensitive (group 1) and those with an allylglycine-induced decrease in GABA-mediated inhibition (group 2). Further, a naturally photosensitive Papio papio (+3 level of photosensitive response) was compared to both groups. Regional brain binding of the specific benzodiazepine receptor ligand, [11C]Ro 15-1788, was not significantly different between groups 1 and 2. In addition, the data from the naturally photosensitive Papio papio did not seem to differ markedly from groups 1 and 2 either. Pharmacological effects of increasing doses of beta-CCM (0.05-3 mg/kg i.v.) and regional benzodiazepine receptor occupancy by the drug were simultaneously studied using electroencephalographic activity recording and positron emission tomography. A positive correlation was observed between the degree of photosensitivity of the baboon and sensitivity to the action of beta-CCM, with increasing convulsant efficacy of beta-CCM in going from group 1 to the naturally photosensitive baboon, then to group 2. Dose-related displacement curves of [11C]Ro 15-1788 binding by beta-CCM revealed that reduction in brain GABA concentration did not modify the inhibitory potency of beta-CCM on [11C]Ro 15-1788 binding in cerebral cortex. This suggests a lack of detectable in vivo allosteric effects of GABA on beta-CCM binding during beta-CCM-induced seizures. Thus, a given dose of beta-CCM displayed increasing pharmacological potency in going from baboons with the lowest photosensitivity to those with the highest, whereas benzodiazepine receptor occupancy by beta-CCM was similar in the cerebral cortex of the different baboons. Conversely, a given level of convulsant activity of beta-CCM was related to a different benzodiazepine receptor occupancy by the drug, depending on the photosensitivity of Papio papio. A given dose of a drug may, thus, have a different pharmacological potency when occupying the same number of receptors, depending on the physiopathological state of the subject.

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