Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Feb;108(2):376–382. doi: 10.1111/j.1476-5381.1993.tb12812.x

The action of SDZ 205,557 at 5-hydroxytryptamine (5-HT3 and 5-HT4) receptors.

R M Eglen 1, R Alvarez 1, L G Johnson 1, E Leung 1, E H Wong 1
PMCID: PMC1907968  PMID: 8448587

Abstract

1. The interaction of the novel antagonist, SDZ 205,557 (2-methoxy-4-amino-5-chloro benzoic acid 2-(diethylamino) ethyl ester), at 5-HT3 and 5-HT4 receptors has been assessed in vitro and in vivo. 2. In guinea-pig hippocampus and in the presence of 0.4 microM 5-carboxamidotryptamine, 5-HT4-mediated stimulation of adenylyl cyclase was competitively antagonized by SDZ 205,557, with a pA2 value of 7.5, and a Schild slope of 0.81. In rat carbachol-contracted oesophagus, 5-HT4-receptor mediated relaxations were surmountably antagonized by SDZ 205,557 with a similar pA2 value (7.3). This value was agonist-independent with the exception of (R)-zacopride, against which a significantly lower value (6.4) was observed. 3. In functional studies of 5-HT3 receptors, SDZ 205,557 exhibited an affinity of 6.2 in guinea-pig ileum compared with 6.9 at binding sites labelled by [3H]-quipazine in NG108-15 cells. In the anaesthetized, vagotomized micropig, SDZ 205,557 produced only a transient blockade of 5-HT4-mediated tachycardia. This contrasted with tropisetron, which was active for over 60 min after administration. The half-lives for the inhibitory responses of SDZ 205,557 and tropisetron were 23 and 116 min, respectively. 4. In conclusion, SDZ 205,557 has similar affinity for 5-HT3 and 5-HT4 receptors. The apparent selectivity observed in guinea-pig is due to the atypical nature of the 5-HT3 receptor in this species. The short duration of action of this novel antagonist may complicate its use in vivo. SDZ 205,557 should, therefore, be used with appropriate caution in studies defining the 5-HT4 receptor.

Full text

PDF
376

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alvarez R., Daniels D. V. A single column method for the assay of adenylate cyclase. Anal Biochem. 1990 May 15;187(1):98–103. doi: 10.1016/0003-2697(90)90423-7. [DOI] [PubMed] [Google Scholar]
  3. Baxter G. S., Craig D. A., Clarke D. E. 5-Hydroxytryptamine4 receptors mediate relaxation of the rat oesophageal tunica muscularis mucosae. Naunyn Schmiedebergs Arch Pharmacol. 1991 May;343(5):439–446. doi: 10.1007/BF00169544. [DOI] [PubMed] [Google Scholar]
  4. Bockaert J., Fozard J. R., Dumuis A., Clarke D. E. The 5-HT4 receptor: a place in the sun. Trends Pharmacol Sci. 1992 Apr;13(4):141–145. doi: 10.1016/0165-6147(92)90051-7. [DOI] [PubMed] [Google Scholar]
  5. Bradley P. B., Engel G., Feniuk W., Fozard J. R., Humphrey P. P., Middlemiss D. N., Mylecharane E. J., Richardson B. P., Saxena P. R. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology. 1986 Jun;25(6):563–576. doi: 10.1016/0028-3908(86)90207-8. [DOI] [PubMed] [Google Scholar]
  6. Buchheit K. H., Gamse R., Pfannkuche H. J. SDZ 205-557, a selective antagonist at 5-HT4 receptors in the isolated guinea pig ileum. Eur J Pharmacol. 1991 Aug 6;200(2-3):373–374. doi: 10.1016/0014-2999(91)90601-l. [DOI] [PubMed] [Google Scholar]
  7. Buchheit K. H., Gamse R., Pfannkuche H. J. SDZ 205-557, a selective, surmountable antagonist for 5-HT4 receptors in the isolated guinea pig ileum. Naunyn Schmiedebergs Arch Pharmacol. 1992 Apr;345(4):387–393. doi: 10.1007/BF00176615. [DOI] [PubMed] [Google Scholar]
  8. Butler A., Elswood C. J., Burridge J., Ireland S. J., Bunce K. T., Kilpatrick G. J., Tyers M. B. The pharmacological characterization of 5-HT3 receptors in three isolated preparations derived from guinea-pig tissues. Br J Pharmacol. 1990 Nov;101(3):591–598. doi: 10.1111/j.1476-5381.1990.tb14126.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Craig D. A., Clarke D. E. Pharmacological characterization of a neuronal receptor for 5-hydroxytryptamine in guinea pig ileum with properties similar to the 5-hydroxytryptamine receptor. J Pharmacol Exp Ther. 1990 Mar;252(3):1378–1386. [PubMed] [Google Scholar]
  10. Dumuis A., Bouhelal R., Sebben M., Cory R., Bockaert J. A nonclassical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system. Mol Pharmacol. 1988 Dec;34(6):880–887. [PubMed] [Google Scholar]
  11. Dumuis A., Gozlan H., Sebben M., Ansanay H., Rizzi C. A., Turconi M., Monferini E., Giraldo E., Schiantarelli P., Ladinsky H. Characterization of a novel 5-HT4 receptor antagonist of the azabicycloalkyl benzimidazolone class: DAU 6285. Naunyn Schmiedebergs Arch Pharmacol. 1992 Mar;345(3):264–269. doi: 10.1007/BF00168685. [DOI] [PubMed] [Google Scholar]
  12. Dumuis A., Sebben M., Bockaert J. The gastrointestinal prokinetic benzamide derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurons. Naunyn Schmiedebergs Arch Pharmacol. 1989 Oct;340(4):403–410. doi: 10.1007/BF00167041. [DOI] [PubMed] [Google Scholar]
  13. Eglen R. M., Swank S. R., Walsh L. K., Whiting R. L. Characterization of 5-HT3 and 'atypical' 5-HT receptors mediating guinea-pig ileal contractions in vitro. Br J Pharmacol. 1990 Nov;101(3):513–520. doi: 10.1111/j.1476-5381.1990.tb14113.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Elswood C. J., Bunce K. T., Humphrey P. P. Identification of putative 5-HT4 receptors in guinea-pig ascending colon. Eur J Pharmacol. 1991 Apr 17;196(2):149–155. doi: 10.1016/0014-2999(91)90421-l. [DOI] [PubMed] [Google Scholar]
  15. Flynn D. L., Zabrowski D. L., Becker D. P., Nosal R., Villamil C. I., Gullikson G. W., Moummi C., Yang D. C. SC-53116: the first selective agonist at the newly identified serotonin 5-HT4 receptor subtype. J Med Chem. 1992 Apr 17;35(8):1486–1489. doi: 10.1021/jm00086a019. [DOI] [PubMed] [Google Scholar]
  16. Idres S., Delarue C., Lefebvre H., Vaudry H. Benzamide derivatives provide evidence for the involvement of a 5-HT4 receptor type in the mechanism of action of serotonin in frog adrenocortical cells. Brain Res Mol Brain Res. 1991 Jun;10(3):251–258. doi: 10.1016/0169-328x(91)90068-9. [DOI] [PubMed] [Google Scholar]
  17. Kaumann A. J. Piglet sinoatrial 5-HT receptors resemble human atrial 5-HT4-like receptors. Naunyn Schmiedebergs Arch Pharmacol. 1990 Nov;342(5):619–622. doi: 10.1007/BF00169055. [DOI] [PubMed] [Google Scholar]
  18. Kaumann A. J., Sanders L., Brown A. M., Murray K. J., Brown M. J. A 5-hydroxytryptamine receptor in human atrium. Br J Pharmacol. 1990 Aug;100(4):879–885. doi: 10.1111/j.1476-5381.1990.tb14108.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kilpatrick G. J., Tyers M. B. Inter-species variants of the 5-HT3 receptor. Biochem Soc Trans. 1992 Feb;20(1):118–121. doi: 10.1042/bst0200118. [DOI] [PubMed] [Google Scholar]
  20. Parker R. B., Waud D. R. Pharmacological estimation of drug-receptor dissociation constants. Statistical evaluation. I. Agonists. J Pharmacol Exp Ther. 1971 Apr;177(1):1–12. [PubMed] [Google Scholar]
  21. Sharif N. A., Wong E. H., Loury D. N., Stefanich E., Michel A. D., Eglen R. M., Whiting R. L. Characteristics of 5-HT3 binding sites in NG108-15, NCB-20 neuroblastoma cells and rat cerebral cortex using [3H]-quipazine and [3H]-GR65630 binding. Br J Pharmacol. 1991 Apr;102(4):919–925. doi: 10.1111/j.1476-5381.1991.tb12277.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shenker A., Maayani S., Weinstein H., Green J. P. Pharmacological characterization of two 5-hydroxytryptamine receptors coupled to adenylate cyclase in guinea pig hippocampal membranes. Mol Pharmacol. 1987 Apr;31(4):357–367. [PubMed] [Google Scholar]
  23. Villalón C. M., den Boer M. O., Heiligers J. P., Saxena P. R. Mediation of 5-hydroxytryptamine-induced tachycardia in the pig by the putative 5-HT4 receptor. Br J Pharmacol. 1990 Aug;100(4):665–667. doi: 10.1111/j.1476-5381.1990.tb14073.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES