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Dive into the research topics where Carl-Gunnar Swahn is active.

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Featured researches published by Carl-Gunnar Swahn.


Psychopharmacology | 1976

Simultaneous determination of the three major monoamine metabolites in brain tissue and body fluids by a mass fragmentographic method

Carl-Gunnar Swahn; Bengt Sandgrde; Frits-Axel Wiesel; G. Sedvall

A mass fragmentographic method for the simultaneous determination of 4-hydroxy-3-methoxyphenylacetic acid (HVA), 4-hydroxy-3-methoxyphenylethylene glycol (MOPEG), and 5-hydroxyindole-3-acetic acid (5-HIAA) was described. Deuterated analogues of the compounds were used as internal standards. The specificity was proved by multiple ion analysis. The experimental error was below 7% when applied to the analysis of human lumbar cerebrospinal fluid, urine, or rat brain tissue. In cerebrospinal fluid the major part of the monoamine metabolites occurred in the free form. In rat brain and human urine considerable amounts of conjugated HVA was found.


Psychosomatic Medicine | 1978

sex Differences in Psychoneuroendocrine Reactions to Examination Stress

Marianne Frankenhaeuser; Aila Collins; Göran Sedvall; Carl-Gunnar Swahn

&NA; Sex differences in adaptation and coping were studied by comparing neuroendocrine and psychological functions in male and female high‐school students during 2‐3 hr of routine school work (control condition) and a 6‐hr matriculation examination (stress condition). In the control condition sex differences were slight and nonsignificant. During examination stress, the urinary excretion of cortisol, adrenaline, noradrenaline, and 3‐methoxy‐4‐hydroxy‐phenylethylene glycol (MOPEG or MHPG) increased in both sexes, but to a consistently greater extent in the male group, significantly so for adrenaline and MOPEG. Both sexes performed equally well in the examination, but self‐reports showed that feelings of success and confidence were common among males, whereas feelings of discomfort and failure dominated in the female group. High discomfort correlated with poor performance in the males but with good performance in the females.


Journal of Cerebral Blood Flow and Metabolism | 1999

Quantification of [11C]FLB 457 Binding to Extrastriatal Dopamine Receptors in the Human Brain

Hans Olsson; Christer Halldin; Carl-Gunnar Swahn; Lars Farde

Positron emission tomography (PET) has hitherto been used to examine D2 dopamine receptor binding in the striatum, a region with a high density of receptors. Research has been hampered by the lack of suitable radioligands for detection of the low-density D2 dopamine receptor populations in the limbic and cortical dopamine systems that are implicated in the patophysiology of schizophrenia. [11C]FLB 457 is a new radioligand with the very high affinity of 20 pmol/L (Ki) for the D2 and D3 dopamine receptor subtypes. This study in eight healthy subjects was designed to evaluate the suitability of [11C]FLB 457 for quantification of extrastriatal D2/D3 dopamine receptors. PET-data were acquired in the three-dimensional mode and the arterial input function was corrected for labeled metabolites. The standard three-compartment model and four derived approaches were applied to calculate and compare the binding potentials. Besides the striatum, conspicuous radioactivity was found in extrastriatal regions such as the thalamus, the anterior cinguli, and the temporal and frontal cortices. The time activity curves could be described by the three compartment model. The different approaches gave similar binding potential values and the rank order between regions was consistent with that found in vitro. The short time of a PET measurement using [11C]FLB 457 (63 minutes) seemed not to be sufficient for reliable determination of the high binding potential in the striatum. These results are of principal importance because they show the potential for PET quantification of minute receptor populations in the human brain.


Psychopharmacology | 1993

PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the D1-dopamine receptor

Per Karlsson; Lars Farde; Christer Halldin; Carl-Gunnar Swahn; Göran Sedvall; Christian Foged; Kristian Tage Hansen; Birte K. Skrumsager

The benzazepines NNC 687 and NNC 756 have in animal studies been described as selective D1-dopamine receptor antagonists. Both compounds have been labeled with11C for examination by positron emission tomography (PET). In the present study central receptor binding was studied in monkeys and healthy men. After IV injection of both radioligands in Cynomolgus monkeys radioactivity accumulated markedly in the striatum, a region with a high density of D1-dopamine receptors. This striatal uptake was displaced by high doses of the selective D1-antagonist SCH 23390 (2 mg/kg) but not by the 5HT2-antagonist ketanserin (1.5 mg/kg) or the selective D2-antagonist raclopride (3 mg/kg). The cortical uptake after injection of [11C]NNC 687 was not reduced in displacement experiments with ketanserin. The cortical uptake of [11C]NNC 756 was reduced in displacement and protection experiments with ketanserin by 24–28% (1.5 mg/kg), whereas no reduction could be demonstrated on striatal uptake. In healthy males both compounds accumulated markedly in the striatum. For [11C]NNC 687 the ratio of radioactivity in the putamen to cerebellum was about 1.5. For [11C]NNC 756 the ratio was about 5. This ratio of 5 for [11C]NNC 756 is the highest obtained so far for PET radioligands for the D1-dopamine receptor.


Synapse | 1997

Effect of reserpine-induced depletion of synaptic dopamine on [11C]raclopride binding to D2-dopamine receptors in the monkey brain.

Nathalie Ginovart; Lars Farde; Christer Halldin; Carl-Gunnar Swahn

Positron emission tomography was used to examine the in vivo binding of [11C]raclopride to D2‐dopamine (DA) receptors in the striatum of two Cynomolgus monkeys after a single dose of reserpine (1 mg/kg, i.v.). A Scatchard procedure was repeated five times to follow D2 receptor density and apparent affinity for 7 weeks after reserpine. Reserpine‐induced depletion of DA lead to a marked increase in [11C]raclopride binding, which was still detectable 20 days after treatment. Scatchard analyses indicated that the measured increase in [11C]raclopride binding reflected an increase in receptor affinity but no evident change in receptor density (Bmax). Thus, the increase in [11C]raclopride binding after reserpine should correspond to a reduced competition with endogenous DA for binding to D2 receptors. The results were used to estimate the DA‐induced D2 occupancy to be about 40% at physiological conditions. Synapse 25:321–325, 1997.


Journal of Labelled Compounds and Radiopharmaceuticals | 1999

Precursor synthesis and radiolabelling of the dopamine D2 receptor ligand [11C]raclopride from [11C]methyl triflate

Oliver Langer; Kjell Någren; Frédéric Dollé; Camilla Lundkvist; Johan Sandell; Carl-Gunnar Swahn; Françoise Vaufrey; Christian Crouzel; Bernard Maziere; Christer Halldin

Desmethyl-raclopride was synthesized via a straightforward, three-step synthetic approach and used for the preparation of [11C]raclopride from [11C]methyl triflate. Conditions for the radiolabelling were optimized to obtain a simple and reproducible procedure suitable for automation. [11C]Raclopride was prepared with an average radiochemical yield of 55–65% (decay corrected, based on starting [11C]methyl triflate) in a total synthesis time (including purification and formulation of product) of 35 min. The radiolabelling procedure used significantly less precursor, avoided the use of DMSO, and was shorter compared to the standard radiolabelling procedure with [11C]methyl iodide. Copyright


Nuclear Medicine and Biology | 1993

[11C]β-CIT, a cocaine analogue. Preparation, autoradiography and preliminary PET investigations

Lars Müller; Christer Halldin; Lars Farde; Per Karlsson; Håkan Hall; Carl-Gunnar Swahn; John L. Neumeyer; Yigong Gao; Milius Richard

beta-CIT (2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane) is a cocaine analogue with a high affinity for the dopamine transporter. [11C] beta-CIT was prepared by N-methylation of nor-beta-CIT with [11C]methyl iodide. The total radiochemical yield of [11C] beta-CIT was 40-50% with an overall synthesis time of 35-40 min. The radiochemical purity was > 99% and the specific radioactivity at the time of injection was about 1000 Ci/mmol (37 GBq/mumol). Autoradiographic examination of [11C] beta-CIT binding in human brains post-mortem demonstrated a high level of specific binding in the striatum. PET examination of [11C] beta-CIT in a Cynomolgus monkey showed a marked accumulation of radioactivity in the striatum. The ratio of radioactivity in the striatum-to-cerebellum approached 5 after 87 min. In a displacement experiment, radioactivity in the striatum but not in the cerebellum, was markedly reduced after injection of unlabelled cocaine. [11C] beta-CIT has a potential as ligand for PET examination of cocaine effects in man.


Life Sciences | 1996

[11C]MDL 100907, a radioligand for selective imaging of 5-HT2A receptors with positron emission tomography

Camilla Lundkvist; Christer Halldin; Nathalie Ginovart; Svante Nyberg; Carl-Gunnar Swahn; Albert A. Carr; Francoise Brunner; Lars Farde

The highly selective 5-HT2A receptor antagonist, MDL 100907 ((R)-(+)-4 -(l-hydroxy-1-(2,3-dimethoxyphenyl)methyl)-N -2-(4-fluorophenylethyl)piperidine), was labeled with 11C for Positron Emission Tomography (PET) studies. After i.v. injection of (R)-(+)-[3-OCH3-11C]MDL 100907 [11C]MDL 100907) in Cynomolgus monkeys a marked accumulation in the 5-HT2A receptor rich neocortical regions was obtained with a neocortex to cerebellum ratio of 3.5-4.5 after 60-80 minutes. In the neocortical regions a transient equilibrium occurred within 40-60 minutes. Radioactivity in the neocortex, but not in the cerebellum, was reduced after injection of ketanserin, indicating that neocortical radioactivity following injection of [11C]MDL 100907 represents specific binding to 5-HT2A receptors. There was no evident effect on neocortical binding after pretreatment with raclopride or SCH 23390. [11C]MDL 100907 has potential to become the first selective radioligand for PET-quantitation of 5-HT2A receptors in the human brain in vivo.


Nuclear Medicine and Biology | 1998

Characterisation of the Appearance of Radioactive Metabolites in Monkey and Human Plasma from the 5-HT1A Receptor Radioligand, [carbonyl-11C]WAY-100635—Explanation of High Signal Contrast in PET and an Aid to Biomathematical Modelling

Safiye Osman; Camilla Lundkvist; Victor W. Pike; Christer Halldin; Julie A. McCarron; Carl-Gunnar Swahn; Lars Farde; Nathalie Ginovart; S. K. Luthra; Roger N. Gunn; Christopher J. Bench; Peter A Sargent; Paul M. Grasby

N-(2-(4-(2-Methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl)++ +cyclohexanecarboxamide (WAY-100635), labelled in its amido carbonyl group with 11C (t1/2 = 20.4 min), is a promising radioligand for the study of brain 5-HT1A receptors with positron emission tomography (PET). Thus, in PET experiments in six cynomolgus monkeys and seven healthy male volunteers, [carbonyl-11C]WAY-100635 was taken up avidly by brain. Radioactivity was retained in regions rich in 5-HT1A receptors, such as occipital cortex, temporal cortex and raphe nuclei, but cleared rapidly from cerebellum, a region almost devoid of 5-HT1A receptors. [Carbonyl-11C]WAY-100635 provides about 3- and 10-fold higher signal contrast (receptor-specific to nonspecific binding) than [O-methyl-11C]WAY-100635 in receptor-rich areas of monkey and human brain, respectively. To elucidate the effect of label position on radioligand behaviour and to aid in the future biomathematical interpretation of the kinetics of regional cerebral radioactivity uptake in terms of receptor-binding parameters, HPLC was used to measure [carbonyl-11C]WAY-100635 and its radioactive metabolites in plasma at various times after intravenous injection. Radioactivity cleared rapidly from monkey and human plasma. Parent radioligand represented 19% of the radioactivity in monkey plasma at 47 min and 8% of the radioactivity in human plasma at 40 min. [Carbonyl-11C]desmethyl-WAY-100635 was below detectable limits in monkey plasma and at most a very minor radioactive metabolite in human plasma. [11C]Cyclohexanecarboxylic acid was identified as a significant radioactive metabolite. In human plasma this maximally represented 21% of the radioactivity at 10 min after radioligand injection. All other major radioactive metabolites in monkey and human plasma were even more polar. No-carrier-added [carbonyl-11C]cyclohexanecarboxylic acid was prepared in the laboratory and after intravenous administration into cynomolgus monkey was shown with PET to give only a low uptake of radioactivity into brain tissue. The acid rapidly gave rise to several radioactive metabolites of higher polarity in plasma. The observed lack of any significant metabolism of [carbonyl-11C]WAY-100635 to highly lipophilic or pharmacologically potent radioactive compounds is consistent with its high signal contrast in primate brain.


Nuclear Medicine and Biology | 1995

Improved synthesis of some commonly used PET radioligands by the use of [11C]methyl triflate

Kjell Någren; Lars Müller; Christer Halldin; Carl-Gunnar Swahn; Pertti Lehikoinen

[11C]Methyl triflate was compared with [11C]methyl iodide as a labelled precursor in the synthesis of some commonly used PET radioligands, L-[11C]deprenyl, [11C]m-hydroxyephedrine (MHED), [11C] beta-CIT, [11C] beta-CFT and [11C]SCH 39166 which have been prepared previously in comparatively low yields from [11C]methyl iodide. A new dopamine reuptake radioligand, [11C] alpha-CIT, was also prepared. The results demonstrate that higher yields are obtained with shorter reaction times, lower reaction temperatures and smaller amounts of precursors with [11C]methyl triflate.

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Kjell Någren

Odense University Hospital

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