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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Eltoprazine suppresses hyperpolarizing responses to serotonin in rat hippocampus.

In this study we report the effects of eltoprazine, a phenylpiperazine derivative with high affinity for 5-hydroxytryptamine1 (5HT1) binding sites, on membrane properties of hippocampal neurons. Intracellular recordings were made from cornus ammoni-1 pyramidal neurons in rat hippocampal slices. Responses to eltoprazine were compared with 5HT-induced responses. Superfusion with 5HT induced a dose-dependent hyperpolarization of the membrane accompanied by a resistance decrease. Eltoprazine evoked membrane changes that were similar to but much weaker than those induced by 5HT. Both the 5HT- and eltoprazine-evoked membrane hyperpolarizations were largely suppressed in the presence of spiperone. The eltoprazine-induced effects persisted in the presence of tetrodotoxin and tetraethylammonium and also when haloperidol and phentolamine were added to the medium, indicating that the small agonistic effects of eltoprazine are not due to an indirect activation of dopamine or alpha adrenergic receptors. Superfusion with eltoprazine furthermore resulted in a marked reduction of the response to concomitantly applied 5HT. Dose-response curves for 5HT were shifted to the right in the presence of eltoprazine, while the maximal response was diminished. Hyperpolarizations induced by baclofen, which presumably activates the same K+ conductance as 5HT, were not significantly reduced by eltoprazine. Our data, added to the previously demonstrated high affinity of eltoprazine for 5HT1 sites, suggest that in the hippocampal cornus ammoni-1 area eltoprazine acts as a partial 5HT1 agonist with a relatively low intrinsic activity but a considerable potency to suppress hyperpolarizing responses to 5HT.[1]


  1. Eltoprazine suppresses hyperpolarizing responses to serotonin in rat hippocampus. Joëls, M., Pennartz, C.M., Sijbesma, H., Schipper, J. J. Pharmacol. Exp. Ther. (1990) [Pubmed]
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