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  • 1
    Electronic Resource
    Electronic Resource
    Simultaneous determination of the three major monoamine metabolites in brain tissue and body fluids by a mass fragmentographic method (1976)
    Springer
    Psychopharmacology 48 (1976), S. 147-152 
    Details
    ISSN: 1432-2072
    Keywords: Mass fragmentography ; 5-Hydroxyindole-3-acetic acid ; 4-Hydroxy-3-methoxyphenylacetic acid ; 4-Hydroxy-3-methoxyphenylethylene glycol ; Cerebrospinal fluid ; Brain ; Urine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00423253
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET) (1997)
    Springer
    European journal of nuclear medicine 24 (1997), S. 1261-1267 
    Details
    ISSN: 1619-7089
    Keywords: Key words: NNC 13-8199 ; Benzodiazepine receptor agonist ; Positron emission tomography ; Carbon-11 ; Bromine-76
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared 76Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [11C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [76Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [76Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590050150
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    In vitro and in vivo characterisation of nor-β-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain (1997)
    Springer
    European journal of nuclear medicine 24 (1997), S. 596-601 
    Details
    ISSN: 1619-7089
    Keywords: Key words: 2β-Carbomethoxy-3β-(4-iodophenyl)nortropane ; Serotonin transporter ; Brain ; Positron emission tomography ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Radiolabelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane (β-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2β-Carbomethoxy-3β-(4-iodophenyl)nortropane (nor-β-CIT) is a des-methyl analogue of β-CIT, which in vitro has tenfold higher affinity (IC50=0.36 nM) to the serotonin transporter than β-CIT (IC50=4.2 nM). Nor-β-CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor-β-CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [125I]nor-β-CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 μM) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [11C]nor-β-CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [11C]nor-β-CIT were 20%–40% higher than those previously obtained with [11C]β-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor-β-CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00841395
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    In vitro and in vivo characterisation of nor-β-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain (1997)
    Springer
    European journal of nuclear medicine 24 (1997), S. 596-601 
    Details
    ISSN: 1619-7089
    Keywords: 2β-Carbomethoxy-3β-(4-iodophenyl)nortrapane ; Serotonin transporter ; Brain ; Positron emission tomography ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Radiolabelled 2β-Cabomethoxy-3β-(4-iodophenyl)tropane (β-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2β-Carbomethoxy-3β-(4-iodophenyl)nortropane (nor-β-CIT) is a des-methyl analogue of β-CIT, which in vitro has tenfold higher affinity (IC50=0.36 nM) to the serotonin transporter than β-CIT (IC50=4.2 nM). Nor-β-CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor-β-CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [125I]nor-β-CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 μM) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [11C]nor-β-CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [11C]nor-β-CIT were 20%–40% higher than those previously obtained with [11C]β-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor-β-CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00841395
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Iodine-123 labelled Z-(R,R)-IQNP: a potential radioligand for visualization of M1 and M2 muscarinic acetylcholine receptors in Alzheimer’s disease (1999)
    Springer
    European journal of nuclear medicine 26 (1999), S. 1482-1485 
    Details
    ISSN: 1619-7089
    Keywords: Key words:Z-(R ; R)-IQNP ; Muscarinic acetylcholine receptors ; Brain ; Single-photon emission tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Z-(R)-1-Azabicyclo[2.2.2]oct-3-yl (R)-α-hydroxy-α-(1-iodo-1-propen-3-yl)-α-phenylacetate (Z-IQNP) has high affinity to the M1 and M2 muscarinic acetylcholine receptor (mAChR) subtypes according to previous in vitro and in vivo studies in rats. In the present study iodine-123 labelled Z-IQNP was prepared for in vivo single-photon emission tomography (SPET) studies in cynomolgus monkeys. SPET studies with Z-[123I]IQNP demonstrated high accumulation in monkey brain (〉5% of injected dose at 70 min p.i.) and marked accumulation in brain regions such as the thalamus, the neocortex, the striatum and the cerebellum. Pretreatment with the non-selective mAChR antagonist scopolamine (0.2 mg/kg) inhibited Z-[123I]IQNP binding in all these regions. The percentage of unchanged Z-[123I]IQNP measured in plasma was less than 10% at 10 min after injection, which may be due to rapid hydrolysis, as has been demonstrated previously with the E-isomer of IQNP. Z-[123I]IQNP showed higher uptake in M2-rich regions, compared with previously obtained results with E-[123I]IQNP. In conclusion, the radioactivity distribution from Z-[123I]IQNP in monkey brain indicates that Z-[123I]IQNP binds to the M1- and M2-rich areas and provides a high signal for specific binding, and is thus a potential ligand for mAChR imaging with SPET.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590050482
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    Paper (German National Licenses)
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