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):387-93. doi: 10.1007/BF00176615.


A selective antagonist for the recently characterized 5-HT4 receptor is lacking. The only surmountable antagonist available, ICS 205-930, is a weak antagonist and is far more potent at 5-HT3-than at 5-HT4 receptors. In this paper, SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester) is characterized as the first potent, selective and surmountable antagonist at 5-HT4 receptors in the isolated guinea pig ileum. SDZ 205-557 was investigated in the non-stimulated and in the field-stimulated guinea pig ileum longitudinal muscle preparation for its affinity for 5-HT4-, 5-HT3-, muscarine-, nicotine- and histamine H1 receptors. The affinity for 5-HT1-, 5-HT2-, alpha 1-, alpha 2- and opiate (mu) receptors was determined by binding assays. SDZ 205-557 was devoid of substantial affinity (pKD values below 5.6) for all receptors investigated except for 5-HT3- and 5-HT4 receptors. At these two receptors, SDZ 205-557 acted as an antagonist without measurable intrinsic activity. At the 5-HT4 receptors of the non-stimulated guinea pig ileum, responses to 5-HT and 5-methoxytryptamine were antagonized by SDZ 205-557 with identical pA2 values of 7.4. The effect of renzapride was also blocked with no significant change in the maximum response; Schild analysis, however, revealed that the interaction was not competitive with an "apparent" pA2 value of 7.6. A pA2 of 6.8 was obtained using zacopride as a contractile agent; this value differed significantly from 7.4, the value obtained for 5-HT and 5-methoxytryptamine.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • 4-Aminobenzoic Acid / pharmacology
  • Animals
  • Electric Stimulation
  • Guinea Pigs
  • Ileum / drug effects
  • In Vitro Techniques
  • Indoles / pharmacology
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Radioligand Assay
  • Serotonin Antagonists* / pharmacology
  • Tropisetron
  • para-Aminobenzoates*


  • Indoles
  • Serotonin Antagonists
  • para-Aminobenzoates
  • 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester
  • Tropisetron
  • 4-Aminobenzoic Acid