Abstract
The mode of antagonism of 5-hydroxytryptamine-induced positive inotropic effects by the highly selective 5-HT4 receptor antagonist SB 207710 (1-butyl4-piperidinyl) methyl 8-amino-7-iodo-1,4-benzodioxan-5-carboxylate was investigated on isolated preparations of human right atrial appendage. SB 207 710 caused concentration-dependent (0.1–10 nmol/l) surmountable antagonism of the effects of 5-hydroxytryptamine with a pKB (mol/l) of 10.1. Due to its high selectivity and affinity, SB 207710 could be a powerful tool for the comparison of human atrial 5-HT4 receptors with 5-HT4 receptors of other organs of man and other species.
References
Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonism. Br J Pharmacol 14:48–58
Brown AM, Young TJ, Patch TL, Cheung CW, Kaumann AJ, Gaster L, King FD (1993) [125I] SB 207710, a potent, selective radioligand for 5-HT4 receptors. Br J Pharmacol 110:9P
Dooley DJ, Bittinger H, Reymann NC (1986) CGP 20712A: A useful tool for quantitative ß1 and ß2 adrenoceptors. Eur J Pharmacol 130:137–139
Dumuis A, Sebben M, Bockaert J (1989) The gastrointestinal prokinetic benzamide derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurons. Naunyn Schmiedeberg's Arch Pharmacol 340:403–410
Grossman CJ, Kilpatrick GJ, Bunce KT (1993) Development of a radioligand assay for 5-HT4 receptors in guinea pig and rat brain. Br J Pharmacol 109:618–624
Kaumann AJ (1986) The ß1-adrenoceptor antagonist CGP 20712A unmasks ß2-adrenoceptors activated by (−)-adrenaline in rat sinoatrial node. Naunyn Schmiedeberg's Arch Pharmacol 332:406–409
Kaumann AJ (1993) Blockade of human atrial 5-HT4 receptors by GR 113 808. Br J Pharmacol 110:1172–1174
Kaumann AJ (1994) Comparative potencies of 5-HT4 receptor antagonists on human right atrium. Br J Pharmacol (in press)
Kaumann AJ, Lemoine H (1987) ß-Adrenoceptor-mediated positive inotropic effect of adrenaline in human ventricular myocardium: quantitative discrepancies with binding and adenylate cyclase stimulation. Naunyn Schmiedeberg's Arch Pharmacol 335:403–411
Kaumann AJ, Sanders L, Brown AM, Murray KJ, Brown MJ (1990) A 5-hydroxytryptamine receptor in human atrium. Br J Pharmacol 100:879–885
Kaumann AJ, Sanders L, Brown AM, Murray KJ, Brown MJ (1991) A 5-HT4-like receptor in human right atrium. Naunyn Schmiedeberg's Arch Pharmacol 344:150–159
Parker SG, Hamburger S, Taylor EM, Kaumann AJ (1993) SB 203186, a potent 5-HT4 receptor antagonist in porcine sinoatrial node and human and porcine atrium. Br J Pharmacol 108:68P
Turconi M, Schiantarelli P, Borsini F, Rizzi CA, Ladinsky H, Donetti A (1991) Azabicycloalkyl benzimidazolones: interaction with serotonergic 5-HT3 and 5-HT4 receptors and therapeutic implications. Drugs of the Future 16:1011–1026
Zerkowski H-R, Broede A, Kunde K, Hillemann S, Schäfer E, Vogelsang M, Michel MC, Broede O-E (1993) Comparison of the positive inotropic effects of serotonin, histamine, angiotensin II, endothelin and isoprenaline in the isolated human right atrium. Naunyn Schmiedeberg's Arch Pharmacol 347:347–352
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kaumann, A.J., Gaster, L.M., King, F.D. et al. Blockade of human atrial 5-HT4 receptors by SB 207710, a selective and high affinity 5-HT4 receptor antagonist. Naunyn-Schmiedeberg's Arch Pharmacol 349, 546–548 (1994). https://doi.org/10.1007/BF00169146
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00169146