Tissue distribution, autoradiography, and metabolism of 4-(2'-methoxyphenyl)-1-[2' -[N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethyl]piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist for positron emission tomography: An In vivo study in rats.
[en] The in vivo behavior of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-[(18)F]fluorobenzamido ]ethyl]-piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist, was studied in awake, freely moving rats. Biodistribution studies showed that the carbon-fluorine bond was stable in vivo, that this compound was able to cross the blood-brain barrier, and that a general diffusion equilibrium could account for the availability of the tracer. The great quantity of highly polar metabolites found in plasma did not contribute to the small amounts of metabolites found in hippocampus, frontal cortex, and cerebellum. Exvivo p-[(18)F]MPPF and in vitro 8-hydroxy-2-(di-n-[(3)H]propylamino)tetralin autoradiography were compared both qualitatively and quantitatively. Qualitative evaluation proved that the same brain regions were labeled and that the p-[(18)F]MPPF labeling is (a) in total agreement with the known distribution of 5-HT(1A) receptors in rats and (b) characterized by very low nonspecific binding. Quantitative comparison demonstrated that the in vivo labeling pattern obtained with p-[(18)F]MPPF cannot be explained by differences in regional blood flow, capillary density, or permeability. The 5-HT(1A) specificity of p-[(18)F]MPPF and binding reversibility were confirmed in vivo with displacement experiments. Thus, this compound can be used to evaluate parameters characterizing 5-HT(1A) binding sites in the brain.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Radiology, nuclear medicine & imaging
Author, co-author :
Plenevaux, Alain ; Université de Liège - ULiège > Centre de recherches du cyclotron
Weissmann, D.
Aerts, Joël ; Université de Liège - ULiège > Centre de recherches du cyclotron
Lemaire, Christian ; Université de Liège - ULiège > Centre de recherches du cyclotron
Brihaye, C.
Degueldre, Christian ; Université de Liège - ULiège > Centre de recherches du cyclotron
Le Bars, Didier; Centre d'Exploration et de Recherche Médicales par Émission de Positons - CERMEP (Lyon)
Comar, Dominique
Pujol, J. F.
Luxen, André ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse - Centre de recherches du cyclotron
Language :
English
Title :
Tissue distribution, autoradiography, and metabolism of 4-(2'-methoxyphenyl)-1-[2' -[N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethyl]piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist for positron emission tomography: An In vivo study in rats.
Publication date :
2000
Journal title :
Journal of Neurochemistry
ISSN :
0022-3042
eISSN :
1471-4159
Publisher :
Blackwell Science, Oxford, United Kingdom
Volume :
75
Issue :
2
Pages :
803-11
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Brihaye C., Lemaire C., and Luxen A. (1994) Robot-assisted synthesis of [18F]altanserin, 4-[18F]fluorotropapride, 6-[18F]fluorodopa and 2-[18F]fluoro-L-tyrosine. J. Labelled Compds. Radiopharm. 35, 160-162.
Cattaneo M. G., Fesce R., and Vicentini L. M. (1995) Mitogenic effect of serotonin in human cell lung carcinoma cells via both 5-HT1A and 5-HT1D receptors. Eur. J. Pharmacol. 291, 209-211.
Fletcher A., Bill D. J., Cliffe I. A., Forster E. A., Jones D., and Reilly Y. (1994) A pharmacological profile of WAY 100635, a potent and selective 5-HT1A receptor antagonist. Br. J. Pharmacol. 112, 91.
Fletcher A., Forster E. A., Bill D. J., Brown G., Cliffe I. A., Hartley J. E., Jones D. E., McLenachan A., Stanhope K. J., Critchley D. J., Childs K. J., Middlefell V. C., Lanfumey L., Corradetti R., Laporte A. M., Gozlan H., Hamon M., and Dourish C. T. (1996) Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonist. Behav. Brain Res. 73, 337-353.
Forster E. A., Cliffe I. A., Bill D. J., Dover G. M., Jones D., Reilly Y., and Fletcher A. (1995) A pharmacological profile of the selective silent 5-HT1A receptor antagonist, WAY-100635. Eur. J. Pharmacol. 281, 81-88.
Gardner J. P., Fornal C. A., and Jacobs B. L. (1997) Effects of sleep deprivation on serotoninergic neuronal activity in the dorsal raphe nucleus of the freely moving cat. Neuropsychopharmacology 17, 72-81.
Gershon M. D., Wade P. R., Kirshgesser A. L., and Tamir H. (1990) 5-HT receptor subtypes outside the central nervous system. Roles in the physiology of the gut. Neuropsychopharmacology 3, 385-395.
Ginovart N., Hassoun W., Le Bars D., Weissmann D., and Leviel V. (2000) In vivo characterization of p-[18F]MPPF, a fluoro analog of WAY-100635 for visualization of 5-HT1A receptors. Synapse 35, 192-200.
Glennon R. A. (1990) Serotonin receptors: clinical implications. Neurosci. Biobehav. Rev. 14, 35-47.
Gozlan H., El Mestikawy S., Pichat L., Glowinski J., and Hamon M. (1983) Identification of presynaptic serotonin receptorusing a new ligand: [3H]-PAT. Nature 305, 140-142.
Gozlan H., Thibault S., Laporte A. M., Lima L., and Hamon M. (1995) The selective 5-HT1A antagonist radioligand [3H]WAY-100635 labels both G-protein-coupled and free 5-HT1A receptors in rat brain membranes. Eur. J. Pharmacol. 288, 173-186.
Hamon M., Lanfumey L., el Mestikawy S., Boni C., Miquel M. C., Bolanos F., Schlechter L., and Gozlan H. (1990) The main features of central 5-HT1 receptors. Neuropsychopharmacology 3, 349-360.
Hervas I. and Artigas F. (1998) Effect of fluoxetine on extracellular 5-hydroxytryptamine in rat brain. Role of 5-HT autoreceptors. Eur. J. Pharmacol 358, 9-18.
Hillver S., Bjork L., Li Y., Svensson B., Ross S., Andèn N., and Hacksell U. (1990) (S)5-Fluoro-8-hydroxy-2-(dipropylamino)tetralin: a putative 5-HT1A receptor antagonist. J. Med. Chem. 33, 1541-1544.
Khawaja X. (1995) Quantitative autoradiographic characterisation of the binding of [3H]WAY-100635, a selective 5-HT1A receptor antagonist. Brain Res. 673, 217-225.
Kia H. K., Miquel M. C., Brisorgueil M. J., Daval G., Riad M., El Mestikawy S., Hamon M., and Verge D. (1996) Immunocytochemical localization of serotonin 1A receptors in the rat central nervous system. J. Comp. Neural. 365, 289-305.
Kostowski W., Plaznik A., and Archer T. (1989) Possible implication of 5-HT1A function for the etiology and treatment of depression. New Trends Exp. Clin. Psychiatry 5, 91-116.
Kung H. F., Stevenson D. A., Zhuang Z. P., Kung M. P., Frederick D., and Hurt S. D. (1996) New 5-HT1A receptor antagonist: [3H]p-MPPF. Synapse 23, 344-346.
Laporte A. M., Lima L., Gozlan H., and Hamon M. (1994) Selective in vivo labelling of brain 5-HT1A receptors by [3H]WAY 100635 in the mouse. Eur. J. Pharmacol. 271, 505-514.
Le Bars D., Lemaire C., Ginovart N., Plenevaux A., Aerts J., Brihaye C., Hassoun W., Leviel V., Mekhsian P., Weissmann D., Pujol J.-F., Luxen A., and Comar D. (1998) High yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a fluoro analog of WAY 100635. Nucl. Med. Biol. 25, 343-350.
Lemaire C., Cantineau R., Guillaume M., Plenevaux A., and Christiaens L. (1991) Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biological behavior in rats. J. Nucl. Med. 32, 2266-2272.
Lestage P., Vitte P. A., Rolinat J. P., Minot R., Broussolle E., and Bobillier P. (1985) A chronic arterial and venous cannulation method for freely moving rats. J. Neurosci. Methods 13, 213-222.
MacLean M. R., Clayton R. A., Templeton A. G., and Morecroft I. (1996) Evidence for 5-HT1-like-receptor-mediated vasoconstriction in human pulmonary artery. Br. J. Pharmacol. 119, 277-282.
Malagié I., Trillat A.-C., Jacquot C., and Gardier A. M. (1995) Effects of acute fluoxetine on extracellular serotonin levels in the raphe: an in vivo microdialysis study. Eur. J. Pharmacol. 286, 213-217.
Meneses A. and Hong E. (1997) Role of 5-HT1A rceptors in acquisition, consolidation and retrieval of learning. CNS Drug Rev. 3, 68-82.
Peroutka S. J. (1995) Serotonin receptor subtypes. Their evolution and clinical relevance. CNS Drugs 4, 18-28.
Pike V. W., McCarron J. A., Lammertsma A. A., Osman S., Hume S. P., Sargent P. A., Bench C. J., Cliffe I. A., Fletcher A., and Grasby P. M. (1996) Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11C]WAY-100635. Eur. J. Pharmacol. 301, R5-R7.
Saudou F. and Hen R. (1994) 5-Hydroxytryptamine receptor subtypes in vertebrates and invertebrates. Neurochem. Int. 25, 503-532.
Saxena P. R. (1995) Serotonin receptors: subtypes, functional response and therapeutic relevance. Pharmacol. Ther. 66, 339-368.
Seifritz E., Stahl M. S., and Gillin J. C. (1997) Human sleep EEG following the 5-HT1A antagonist pindolol: possible disinhibition of raphe neuron activity. Brain Res. 759, 84-91.
Shiue C.-Y., Shiue G. G., Mozley P. D., Kung M.-P., Zhuang Z.-P., Kim H.-J., and Kung H. F. (1997) p-[18F]MPPF: a potential radioligand for PET studies of 5-HT1A receptors in humans. Synapse 25, 147-154.
Thielen R. J., Fangon N. B., and Frazer A. (1996) 4-(2′-Methoxyphenyl)-1-[2′-[N-(2″-pyridinyl)-p-iodobenzamido] ethyl]piperazine and 4-(2′-methoxyphenyl)-1-[2′-[N-(2″-pyridinyl)-p- fluorobenzamido]ethyl]piperazine, two new antagonists at pre-and postsynaptic serotonin-1A receptors. J. Pharmucol. Exp. Ther. 277, 661-670.
Van Wijngaarden I., Tulp M. T. M., and Soudijn W. (1990) The concept of selectivity in 5-HT receptor research. Eur. J. Pharmacol. 188, 301-312.
Vergé D., Daval G., Marcinkiewicz M., Patey A., El Mestikawy S., Gozlan H., and Hamon M. (1986) Quantitative autoradiography of multiple 5-HT1 receptor subtypes in brain of control or 5,7-dihydroxytryptamine-treated rats. J. Neurosci. 6, 3474-3482.
Weissmann D., Mach E., Magre J., Demassey Y., and Pujol J.-F. (1985) Evidence for the localization of 5-HT1A binding sites on serotonin containing neurons in the raphe dorsalis and raphe centralis nuclei of the rat brain. Neurochem. Int. 7, 1061-1072.
Zhuang Z. P., Kung M. P., and Kung H. F. (1994) Synthesis and evaluation of 4-(2′-methoxyphenyl)-1-[2′-[N-(2″-pyridinyl)-p-iodobenzamido] ethyl]piperazine (p-MPPI): a new iodinated 5-HT1A ligand. J. Med. Chem. 37, 1406-1407.