Attenuation of ischemic efflux of endogenous amino acids by the novel 5-HT(1A)/5-HT(2) receptor ligand adatanserin.

Abstract

Using sodium azide (NaN3)-induced anoxia plus aglycaemia as a model of chemically-induced ischemia in the hippocampal slice, we have evaluated the effects of the novel 5-HT(1A) partial agonist/5-HT(2) receptor antagonist adatanserin and the 5-HT(1A) receptor agonist BAYx3702 on the efflux of endogenous glutamate, aspartate and GABA. BAYx3702 (10-1000 nM) produced a significant (P<0.05) dose-related attenuation of ischemic efflux of both glutamate and GABA with maximum decrease being observed at 100 nM (73 and 69%, respectively). This attenuation was completely reversed by the addition of the 5-HT(1A) antagonist, WAY-100635 (100 nM). Similarly, adatanserin (10-1000 nM) produced a significant (P<0.05) dose-related attenuation in glutamate and GABA efflux with a maximum of 72 and 81% at 100 nM, respectively. This effect was completely reversed by the 5-HT(2A/C) receptor agonist, DOI but unaffected by WAY-100635. The 5-HT(2A) receptor antagonist MDL-100907 produced a comparable attenuation of glutamate when compared to adatanserin, while the 5-HT(2C) receptor antagonist, SB-206553, had no effect on ischemic efflux. None of these compounds significantly altered aspartate efflux from this preparation. In conclusion, the 5-HT(1A) receptor partial agonist 5-HT(2) receptor antagonist, adatanserin is able to attenuate ischemic amino acid efflux in a comparable manner to the full 5-HT(1A) agonist BAYx3702. However, in contrast to BAYx3702, adatanserin appears to produce it effects via blockade of the 5-HT(2A) receptor. This suggests that adatanserin may be an effective neuroprotectant, as has been previously demonstrated for full 5-HT(1A) receptor agonists such as BAYx3702.

• Authors: L A Dawson, J Galandak, S Djali
• Journal: Neurochemistry international (Neurochem Int) Vol. 40 Issue 3 Pg. 203-9 (Mar 2002) ISSN: 0197-0186 [Print] England
• PMID: 11741003 (Publication Type: Journal Article)

Chemical References

• Amino Acids
• Fluorobenzenes
• Indoles
• Ligands
• Piperazines
• Piperidines
• Pyridines
• Pyrimidines
• Receptor, Serotonin, 5-HT2A
• Receptor, Serotonin, 5-HT2B
• Receptors, Serotonin
• Receptors, Serotonin, 5-HT1
• Serotonin Antagonists
• Serotonin Receptor Agonists
• WY 50324
• SB 206553
• volinanserin

Topics

• Amino Acids (metabolism)
• Animals
• Brain Ischemia (metabolism)
• Fluorobenzenes (pharmacology)
• Hippocampus (blood supply, drug effects, metabolism)
• In Vitro Techniques
• Indoles (pharmacology)
• Ligands
• Male
• Piperazines (pharmacology)
• Piperidines (pharmacology)
• Pyridines (pharmacology)
• Pyrimidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Serotonin, 5-HT2A
• Receptor, Serotonin, 5-HT2B
• Receptors, Serotonin (metabolism)
• Receptors, Serotonin, 5-HT1
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)