Summary
Because tryptamine derivatives typically bind at multiple populations of 5-HT receptors, they are not normally considered as templates for the design of site-selective serotonergic agents. Taking advantage of the proposal that 5-HT3 receptors are ligand-gated ion channel receptors, and that such receptors usually accept positively charged ligands, we synthesized and evaluated the N,N,N-trimethyl quaternary amine analog of serotonin (5HTQ), 5-HTQ binds at 5-HT3 receptors with ten times the affinity of 5-HT and displays considerable selectivity relative to the other populations of 5-HT receptors. Although 5-HTQ may not readily penetrate the blood-brain barrier, limiting its application for in vivo investigations, it should be useful for in vitro studies.
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References
Barnes, N. M., Costal!, B., and Naylor, R. J. (1988), [3H]Zacopride: Ligand for the identification of 5-HT3 recognition sites. J, Pharm. Pharmacol. 40: 548–551.
Fozard, J. R. (1990), 5-HT3 Receptors. In: Paoletti, R., Vanhoutte, P. M., Brunello, N., and Maggi, F. M. (eds.), Serotonin: From Cell Biology to Pharmacology and Therapeutics. Dordrecht: Kluwer, pp. 331 – 338.
Glennon, R. A., Titeler, M., Seggel, M. R., and Lyon, R. A. (1987), N-Methyl derivatives of the 5-HT2 agonist 1-(4-bromo-2,5-dimethoxypheny1)-2-aminopropane. J. Med. Chem. 30: 930–932.
Glennon, R. A., Titeler, M., Lyon, R. A., and Slusher, M. (1988), N,N-di-n-propylserotonin: Binding at serotonin binding sites and a comparison with 8-hydroxy-2-(di-n-propylamino)tetralin. J. Med. Chem. 31: 867–870.
Glennon, R. A., Westkaemper, R. B., and Bartyzel, P. (1990a), Medicinal chemistry of serotonergic agents. In: Peroutka, S. J. (ed.), Serotonin Receptor Subtypes. New York: Wiley-Liss, in press.
Glennon, R. A., Chaurasia, C., Titeler, M., and Weisberg, E. L. (1990b), Development of a high-affinity tryptamine analog for 5-HT2 sites. Second IUPHAR Satellite Meeting on Serotonin, Basel, Switzerland. July 11–13, 1990, Abs p. 50.
Ismaiel, A. M., Titeler, M., Miller, K. J., Smith, T. S., and Glennon, R. A. (1990), 5-HTI and 5-HT2 Binding profiles of the serotonergic agents x-methylserotonin and 2-methylserotonin. J. Med. Chem. 33: 755–758.
Kilpatrick, G. J., Jones, B. J., and Tyres, M. B. (1990), Brain 5-HT3 Receptors. In: Paoletti, R., Vanhoutte, P. M., Brunello, N., and Maggi, F. M. (eds.), Serotonin: From Cell Biology to Pharmacology and Therapeutics. Dordrecht: Kluwer, pp. 339 - 345.
Naiman, N. A., Lyon, R. A., Bullock, A. E., Rydelek, L. Y., Titeler, M., and Glennon, R. A. (1989), 2-Alkylaminotetralin derivatives: Interaction with 5-HT,A binding sites. J. Med. Chem. 32: 253–256.
Peroutka, S. J., and Hamik, A. (1988), [3H]Quipazine labels 5-HT3 recognition sites in rat cortical membranes. Eur. J. Pharmacol. 148: 297–299.
Richardson, B. P., Engel, G., Donatsch, P., and Stadler, P. A. (1985), Identification of 5-hydroxytryptamine M-receptor subtypes and their specific blockade by a new class of drugs. Nature 316: 126 – 131.
Wallis, D. I., and Nash, H. L. (1980), The action of methylated derivatives of 5-hydroxytryptamine at ganglionic receptors. Neuropharmacology 19: 465 – 472.
Watling, K. J., Aspley, S., Swain, C. J., and Saunders, J. (1988), [3H]-Quaternized ICS, 205-930 labels 5-HT3 receptor binding sites in rat brain. Eur. J. Pharmacol. 149: 397–398.
Wieland, H., Konz, W., and Mittasch, H. (1934), Die Konstitution von Bufotenin und Bufotenidin. Justus Liebigs Ann. Chem. 513: 1–25.
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© 1991 Birkhäuser Verlag Basel/Switzerland
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Glennon, R.A., Peroutka, S.J., Dukat, M. (1991). Binding Characteristics of a Quaternary Amine Analog of Serotonin: 5-HTQ. In: Fozard, J.R., Saxena, P.R. (eds) Serotonin: Molecular Biology, Receptors and Functional Effects. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7259-1_17
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DOI: https://doi.org/10.1007/978-3-0348-7259-1_17
Publisher Name: Birkhäuser Basel
Print ISBN: 978-3-0348-7261-4
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