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R Camsonne

Publications and source records attributed to R Camsonne.

At least 19 recordsLinked to original sources
PubMed2003

Short-term pharmacokinetics and brain distribution of mecamylamine as a preliminary to carbon-11 labeling for nicotinic receptor investigation.

As a preliminary to development and evaluation of labeled mecamylamine as a potential in vivo imaging ligand for human central nicotinic receptors (nAchRs), this work was intended to determine whether the pharmacokinetic properties of mecamylamine are suitable for experimental studies using (11)C-radiolabeled mecamylamine preliminary to positron emission tomography (PET) in humans. An original gas chromatographic method for rapid and simple determination of mecamylamine in biological samples was developed and validated (within run precision, 3.8-5.2%; between assay variation, 5.3-6.9%; assay accuracy, 5.6-11.8%). The results of the pharmacokinetic investigation in the rat demonstrated a very fast clearance of mecamylamine from blood [half-life, 1.2 h; clearance (CL), 1.2 L/kg/h) concomitant with an uptake that was higher in kidney, intermediate in lung, and lower in heart, liver, and brain. Brain tissue kinetics of mecamylamine showed a similar pattern for all the regions, with a rapid increase followed by a plateau after 15 min. This plateau differed according to the region of the brain; it was higher in colliculi, hippocampus, and cortex (area of high density of nAchRs) than in cerebellum or white matter (area with a limited population of nAchRs). No other lipophilic metabolites that were able to disturb the specific binding to nAchRs were identified during the investigation. Thus, mecamylamine shows peculiar qualities making it a good candidate for carbon-11 labeling for experimental studies in view of final PET imaging.

Animals↗
PubMed1998

[Xenografts: clinical trials and perspectives].

Despite the reticence of certain prominent scientists, there will be no moratorium on clinical xenotransplantation in the USA and a limited number of well-controlled trials will be enabled. There has already been some advances in cell and tissue xenografts with encapsulated porcine pancreas cells and porcine foetal neurones in patients with diabetes and Parkinson's disease. However, because of some porcine viruses are able to develop in human tissues, current and planned trials have been interrupted until routine viral detection tests are available. Several attempts have been made in the past, with animal organs (kidney, heart, liver) from various non-human primate species and conventional immunotherapy without success. Another major question now, is the choice of the animal donor species. Phylogenetically dose to man, non-human primates would be a right and logical choice. But, because of their procurement problems, it is likely that most future trials will be conducted with porcine organs from more performant transgenic animals, more powerful immunosuppressors and new therapeutic strategies based on the natural tolerance mechanisms.

Animals↗
PubMed1993

Positron emission tomographic studies of [11C]MDL 72222, a potential 5-HT3 receptor radioligand: distribution, kinetics and binding in the brain of the baboon.

The drug MDL 72222, a selective 5-HT3 receptor antagonist, was labelled with 11C and evaluated for distribution kinetics in brain and in vivo binding to 5-HT3 receptors using cold MDL 72222 challenge and positron emission tomography (PET), in three anaesthetized baboons. After tracer doses of [11C]MDL 72222 (i.v. bolus), 11C radioactivity was equally partitioned between plasma and blood cells and readily crossed the blood-brain barrier; it was distributed heterogeneously into 17 different structures of the brain. The kinetic curves for 11C in tissue showed a rapid initial uptake, followed by a slower ascending phase, up to about the twentieth minute and by a plateau, until the end of experiment (90 min). The plateau values indicated marked uptake in brain which, however, varied according to the region considered. In inhibition studies with cold MDL 72222 (1 mg.kg-1) as pretreatment, co-injection or displacement, no clear-cut effects on the kinetics of [11C] MDL 72222 in brain were detected in any region, including those known to be rich in 5-HT3 receptors. These observations suggest that specific binding to 5-HT3 receptors was not detectable in brain in vivo, because of the high lipophilicity (thus a great capacity for non-specific binding) of MDL 72222. These negative findings may also result from both the possible suboptimal affinity of MDL 72222 for 5-HT3 receptors in vivo and the relatively low density of 5-HT3 receptors present only in selected areas of the mammalian brain. This study is a step in the search of selective 5-HT3 receptor radioligands, adequate for in vivo applications. Slow clearance of [11C]MDL 72222 from brain tissue in baboons, should be accounted for in clinical pharmacokinetic investigations for optimal posology considerations.

Animals↗
PubMed1992

Synthesis and regional rat brain distribution of [11C]MDL 72222: a 5HT3 receptor antagonist.

MDL 72222, an antagonist of 5HT3 receptors, was labeled with a specific radioactivity of 340-400 mCi/mumol by alkylation of the nor-precursor with [11C]CH3I. The yield of the synthesis, starting from [11C]methyliodide to the purified product and corrected for decay, was good approximately 70-75%. After i.v. injection, [11C]MDL 72222 diffuses readily in the central nervous system but is not detected as metabolites in brain and blood, during 1 h study carried out in rats. The time course and distribution of [11C]MDL 72222 was assessed in various organs (liver, lung, kidney, heart, whole brain) and in blood; the organ uptake was rapid and large; the highest accumulation was found in the lung. The regional brain distribution shows initial uptake and subsequent retention of tracer in favor of the cerebral cortex. The level of brain radioactivity was not reduced by pretreatment with a 1000-fold excess of unlabeled MDL 72222. These results suggest that [11]MDL 72222 is of limited interest for 5HT3 receptor binding studies in brain in vivo, presumably mainly because of large non-specific binding.

Animals↗
PubMed1991

Brain kinetics and specific binding of [11C]PK 11195 to omega 3 sites in baboons: positron emission tomography study.

We characterized, in vivo, using positron emission tomography in baboons, the kinetics and specific binding of i.v. injected [11C]PK 11195 to omega 3 sites in the brain. Following immediate access to brain tissue, the brain kinetics of [11C] K 11195 showed a slow elimination for the 60 min of study. Both coinjection and pulse-chase (at t = 8 min) with saturating amounts of cold PK 11195 immediately enhanced the availability of radiotracer to brain tissue, but also markedly increased the rate of washout. These effects presumably reflect displacement or inhibition of specifically bound [11C]PK 11195 to both peripheral and central omega 3 sites, respectively. These results indicate that [11C]PK 11195 has easy access and binds with moderate specificity to the normal primate brain in vivo.

Animals↗
PubMed1989

Quinidine disposition in relation to antipyrine elimination and debrisoquine phenotype in alcoholic patients with and without cirrhosis.

Single dose disposition of oral quinidine (400 mg sulfate) was studied in a control group of subjects (No. = 6) and in hospitalized alcoholic patients involving one group with (No. = 6) and one group without (No. = 11) hepatic cirrhosis. All subjects also underwent an antipyrine and a debrisoquine test. Patients with cirrhosis had a prolonged elimination half-life (29.5 +/- 5.9 h) and low clearance (24 +/- 7 ml.kg-1.h-1) of antipyrine and also a considerably higher debrisoquine metabolic ratio (18.8 +/- 3.3) than the controls, whereas the alcoholics without cirrhosis had metabolic patterns for these two test compounds comparable to those seen in the controls (antipyrine half-life: 8.8 +/- 1.1 h and 9.8 +/- 2.0 h; debrisoquine metabolic ratio: 3.6 +/- 0.7 and 3.8 +/- 1.2 for alcoholics and controls respectively). In patients with cirrhosis the apparent elimination half-life of quinidine was longer (12.8 +/- 1.8 h) whereas after oral administration clearance of quinidine (15.6 +/- 3.5 l.h-1) and quinidine/3-hydroxyquinidine ratio (9.9 +/- 2.1) were not different from controls (quinidine clearance: 13.45 +/- 1.9 l.h-1; quinidine/3-hydroxyquinidine: 10.3 +/- 2.7). A possible change in distribution patterns of quinidine in cirrhotics may explain these findings.

Adult↗
PubMed1985

Elimination kinetic of high polar metabolites pool of quinidine from human serum.

The elimination half-life of high polar metabolites pool of quinidine (t1/2 beta = 6.1 h) has been determined in a quinidine phenobarbiturate intoxicated patient after the complete elimination of quinidine (its precursor) from blood. It is equivalent to the generally accepted t1/2 beta of quinidine (6.1 +/- 1.8 h) but substantially different from the t1/2 beta "hybrid" of 3-hydroxyquinidine (10.0 h) determined in therapeutic conditions in which 3-hydroxyquinidine coexists with quinidine in blood. With regard to the low serum level of quinidine and strong ECG impairments, it is speculated that high polar metabolites of quinidine taken as a whole could be involved in this life threatening intoxication.

Barbiturates↗
PubMed1984

A simple fluorescence high-performance liquid chromatographic assay for dihydroquinidine in serum.

A simple and rapid reversed-phase C-18 high-performance liquid chromatography (HPLC) assay without a prior extraction step for dihydroquinidine (HQD) in serum is described. The method is selective and useful for monitoring HQD and its presumed metabolites, quinidine (QD), N-oxide QD, 3-hydroxy QD (3-OHQD), and 10-11-diol QD. The detection limit for HQD was 0.2 +/- 0.1 mg/L, and the peak heights--concentration curve was linear between 0.5 and 10.0 mg/L. The coefficients of variation within and between runs were identical, 5.0 +/- 1.5%. A 100 +/- 2.5% recovery was obtained by direct injection into the chromatograph of the supernatant following acetonitrile protein precipitation. The total assay time was less than 15 min.

Blood Proteins↗