Characterization of the novel 5-HT3 antagonists MDL 73147EF (dolasetron mesilate) and MDL 74156 in NG108-15 neuroblastoma x glioma cells.

Abstract

In radioligand binding experiments, MDL 73147EF and MDL 74156 inhibited the binding of [3H]GR65630 to 5-hydroxy-tryptamine3 (5-HT3) binding sites on membranes prepared from NG108-15 neuroblastoma x glioma cells. The calculated dissociation constants (KI) were 20.03 +/- 6.58 and 0.44 +/- 0.18 nM, respectively (means +/- S.E.M., n = 6 and 9, respectively). Application of 5-HT (10-50 microM) to voltage-clamped NG108-15 cells elicited a rapidly desensitizing inward membrane current, characteristic for the activation of 5-HT3 receptors. The 5-HT-induced membrane current was suppressed in a reversible, concentration-dependent manner by MDL 73147EF and MDL 74156EF. The concentrations required to block half the 5-HT response (IC50) were 3.8 and 0.1 nM, respectively. It is concluded that both compounds are potent and reversible antagonists at 5-HT3 receptors in this neuroblastoma cell line.

• Authors: P H Boeijinga, M Galvan, B M Baron, M W Dudley, B W Siegel, A L Slone
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 219 Issue 1 Pg. 9-13 (Aug 14 1992) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1397053 (Publication Type: Journal Article)

Chemical References

• Imidazoles
• Indoles
• Quinolizines
• Receptors, Serotonin
• Serotonin Antagonists
• GR 65630
• dolasetron
• hydrodolasetron

Topics

• Animals
• Binding, Competitive
• Glioma (pathology)
• Hybrid Cells
• Imidazoles (metabolism)
• Indoles (metabolism, pharmacology)
• Membrane Potentials (drug effects)
• Mice
• Neuroblastoma (pathology)
• Quinolizines (metabolism, pharmacology)
• Rats
• Receptors, Serotonin (metabolism)
• Serotonin Antagonists (pharmacology)