Synthesis and radioligand binding studies of C-5- and C-8-substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums as SK channel blockers related to N-methyl-laudanosine and N-methyl-noscapine
[en] The synthesis and the 125 I-apamin binding studies of original C-5- and C-8-substituted 143,4-dimethoxy-benzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums and 1-(3,4-dimethoxy-benzyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridiniums were performed in order to find a reversible and selective SK channel blocker structurally related to N-methyl-laudanosine and N-methyl-noscapine. A bulky alkyl substituent in the C-8 position of the tetrahydroisoquinoline produces a clear increase in the affinity for the apamin sensitive binding sites. The presence of an electron-withdrawing group in the C-5 and C-8 positions is not a suitable substitution for the affinity of drugs structurally related to N-methyl-laudanosine. Thiophenic analogues and 8-methoxy derivatives possess a poor affinity for the apamin sensitive binding sites. Electrophysiological studies performed with the most effective compound showed a blockade of the apamin sensitive afterhyperpolarization in rat dopaminergic neurons.
Scuvée-Moreau, Jacqueline ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie - Département des sciences biomédicales et précliniques
Seutin, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Liégeois, Jean-François ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Language :
English
Title :
Synthesis and radioligand binding studies of C-5- and C-8-substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums as SK channel blockers related to N-methyl-laudanosine and N-methyl-noscapine
Publication date :
28 July 2005
Journal title :
Journal of Medicinal Chemistry
ISSN :
0022-2623
eISSN :
1520-4804
Publisher :
Amer Chemical Soc, Washington, United States - Washington
Sah, P. Ca2+-activated K+ current in neurons: Types, physiological roles and modulation. Trends Neurosci. 1996, 19, 150-154.
Vergara, C.; LaTorre, R.; Marrion, N. V.; Adelman, J. P. Calcium-activated potassium channels. Curr. Opin. Neurobiol. 1998, 8, 321-329.
Kolher, M.; Hirschberg, B.; Bond, C. T.; Kinzie, J. M.; Marrion, N. V.; Maylie, J.; Adelman, J. P. Small-conductance, calcium-activated potassium channels from mammalian brain. Science 1996, 273, 1709-1714.
Stocker, M.; Krause, M.; Pedarzani, P. An apamin-sensitive Ca 2+-activated K+ current in hippocampal pyramidal neurons. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 4662-4667.
Stocker, M.; Pedarzani, P. Differential distribution of three Ca 2+-activated K+ channel subunits SK(1-3) in the adult rat central nervous system. Mol. Cell. Neurosci. 2000, 15, 476-493.
Messier, C.; Mourre, C.; Bontempi, B.; Sif, J.; Lazdunski, M.; Destrade, C. Effect of apamin, a toxin that inhibits calcium-dependent potassium channels, on learning and memory processes. Brain Res. 1991, 551, 322-326.
Deschaux, O.; Bizot, J. C.; Goyffon, M. Apamin improves learning in an object recognition task in rats. Neurosci. Lett. 1997, 222, 159-162.
Ikonen, S.; Riekkinen, P., Jr. Effect of apamin on memory processing of hippocampal-lesioned mice. Eur. J. Pharmacol. 1999, 382, 151-156.
Van der Staay, F. J.; Fanelli, R. J.; Blokland, A.; Schmidt, B. H. Behavioral effects of apamin, a selective inhibitor of the SKCa channel, in mice and rats. Neurosci. Biobehav. Rev. 1999, 23, 1087-1110.
Fournier, C.; Kourrich, S.; Soumireu-Mourat, B.; Mourre, C. Apamin improves reference memory but not procedural memory in rats by blocking small conductance Ca2+-activated K+channels in an olfactory discrimination task, Behav. Brain Res. 2001, 121, 81-93.
Pedarzani, P.; Mosbacher, J.; Rivard, A.; Cingolani, L. A.; Oliver, D.; Stocker, M.; Adelman, J. P.; Fakler, B. Control of electrical activity in central neurons by modulating the gating of small conductance Ca 2+-activated K+ channels. J. Biol. Chem. 2001, 276, 9762-9769.
Steketee, J. D.; Kalavas, P. W. Effect of microinjections of apamin into the A10 dopamine region of rats: A behavioural and neurochemical analysis. J. Pharmacol. Exp. Ther. 1990, 254, 711-719.
Shepard, P. D.; Bunney, B. S. Repetitive firing properties of putative dopamine-containing neurons in vitro: Regulation by an apamin-sensitive Ca 2+-activated K+ conductance. Exp. Brain Res. 1991, 86, 141-150.
Seutin, V.; Johnson, S. V.; North, R. A. Apamin increases NMDA-induced burst firing of rat mesencephalic dopamine neurons. Brain Res. 1993, 630, 341-344.
Vincent, J. P.; Schweitz, H.; Lazdunski, M. Structure-function relationships and site of action of apamin, a neurotoxic polypeptide of bee venom with an action on the central nervous system. Biochemistry 1975, 14, 2521-2525.
Zerrouk, H.; Lavaba-Djerbari, F.; Fremont, V.; Meki, A.; Darbon, H.; Mansuelle, P.; Oughuideni, R.; Van Rietschoten, J.; Rochat, H.; Martin-Eauclaire, M. F. Characterization of PO1, a new peptide ligand of the apamin-sensitive Ca2+-activated K+ channel. Int. J. Pept. Protein Res. 1996, 48, 514-521.
Campos Rosa, J.; Galanakis, D.; Piergentili, A.; Bhandari, K.; Ganellin, C. R.; Dunn, P. M.; Jenkinson, D. H. Synthesis, molecular modelling, and pharmacological testing of bis-quinolinium cyclophanes: Potent, nonpeptidic blockers of the apamin-sensitive Ca2+-activated K+ channel. J. Med. Chem. 2000, 43, 420-431.
Johnson, S. W.; Seutin, V. Bicuculline methiodide potentiates NMDA-dependent burst firing in rat dopamine neurons by blocking apamin-sensitive Ca2+-activated K+ currents. Neurosci. Lett. 1997, 231, 13-16.
Scuvée-Moreau, J.; Liégeois, J.-F.; Massotte, L.; Seutin, V. Methyl-laudanosine: A new pharmacological tool to investigate the function of small-conductance Ca2+-activated K+ channels. J. Pharmacol. Exp. Ther. 2002, 302, 1176-1183.
Scuvée-Moreau, J.; Boland, A.; Graulich, A.; Van Overmeire, L.; D'hoedt, D.; Graulich-Lorge, F.; Thomas, E.; Abras, A.; Stocker, M.; Liégeois, J.-F.; Seutin, V. Electrophysiological characterization of the SK channel blockers methyl-laudanosine and methyl-noscapine in cell lines and rat brain slices. Br. J. Pharmacol. 2004, 143, 753-764.
Brown, W. D.; Gouliaev, A. H. Bromination of isoquinoline, quinoline, quinazoline and quinoxaline in strong acid. Synthesis 2002, 83-86.
Osborn, A. R.; Schofield, K.; Short, L. N. Studies of the amino-isoquinolines, -cinnolines, and -quinazolines. J. Chem. Soc. 1956, 4191-4206.
Hendrickson, J. B.; Rodriguez, C. An efficient synthesis of substituted isoquinolines. J. Org. Chem. 1983, 48, 3344-3346.
Graulich, A.; Liégeois, J.-F. A rapid synthesis of thieno[2,3-c]-pyridine and 2-substituted thieno[2,3-c]pyridines. Synthesis 2004, 1935-1937.
Jones, G. The synthesis of some dimethyl- and ethyl-isoquinolines. J. Chem. Soc. 1960, 1918-1923.
Popp, F. D. Developments in the chemistry of Reissert compounds (1968-1978). Adv. Heterocycl. Chem. 1979, 24, 187-214.
Ruchirawat, S.; Phadungkul, N.; Chuankamnerdkarn, M.; Thebtaranonth, C. A versatile synthesis of Reissert compounds. Heterocycles 1977, 6, 43-46.
Bass, R. J.; Popp, F. D.; Kant, J. The thieno[2,3-c]pyridine Reissert compound. J. Heterocycl. Chem. 1984, 21, 1119-1120.
Seutin, V.; Johnson, S. W. Recent advances in the pharmacology of quaternary salts of bicuculline. Trends Pharmacol. Sci. 1999, 20, 268-270.
Graulich, A.; Scuvée-Moreau, J.; Seutin, V.; Liégeois, J.-F. Synthesis and biological evaluation of N-methyl-laudanosine iodide analogues as potential SK channel blockers. Bioorg. Med. Chem. 2005, 13, 1201-1209.
Wadsworth, J. D. F.; Doorty, K. B.; Strong, P. N. Comparable 30-kDa apamin binding polypeptides may fulfill equivalent roles within putative subtypes of small conductance Ca2+-activated K+ channels J. Biol. Chem. 1994, 269, 18053-18061.
Finlayson, K.; McLuckie, J.; Hern, J.; Aramori, I.; Olverman, H. J.; Kelly, J. S. Characterization of [125I]-apamin binding sites in rat brain membranes and HEK293 cells transfected with SK channel subtypes. Neuropharmacology 2001, 41, 341-350.
Granier, C.; Pedroso Muller, E.; Van Rietschoten, J. Use of synthetic analogues for a study on the structure-activity relationship of apamin. Eur. J. Biochem. 1978, 82, 293-299.
Habermann, E. Apamin. Pharmacol. Ther. 1984, 25, 255-270.
Galanakis, D.; Ganellin, C. R.; Chen, J.-Q.; Gunasekera, D.; Dunn, P. M. Bis-quinolinium cyclophanes: Towards a pharmacophore model for the blockade of apamin-sensitive SKCa channels in sympathetic neurons. Bioorg. Med. Chem. Lett. 2004, 14, 4231-4235.
Hartree, E. F. Determination of protein: A modification of the Lowry method that gives a linear photometric response. Anal. Biochem. 1972, 48, 422-427.
