当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > Augmentation with a 5-HT(1A), but not a 5-HT(1B) receptor antagonist critically depends on the dose of citalopram.

Augmentation with a 5-HT(1A), but not a 5-HT(1B) receptor antagonist critically depends on the dose of citalopram.

Abstract：

:Pharmacokinetic and pharmacodynamic parameters of the selective serotonin reuptake inhibitor 1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-5-phtalancarbonitril (citalopram) were determined in order to find optimal conditions for augmentation of its effect on extracellular serotonin [5-hydroxytryptamine (5-HT)] through blockade of 5-HT(1A) and 5-HT(1B) autoreceptors. Citalopram dose-dependently (0.3-10 micromol/kg s.c.) increased serotonin levels in ventral hippocampus of conscious rats. At plasma levels above approximately 0.15 microM, the effect of citalopram on extracellular 5-HT was augmented by both a 5-HT(1A) [N-[2-[4-(2-mehoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridil) cyclohexa necarboxamide trihydrochloride (Way 100635), 1 micromol/kg s.c.] and a 5-HT(1B) receptor antagonist (2'-methyl-4'-(5-methyl-[1,2, 4]oxadiazol-3-yl)biphenyl-4-carboxylic acid [4-methoxy]-3-(4-methylpiperazin-1-yl)phenyl]amide (GR 127935), 1 micromol/kg s.c.). However, at plasma levels of the selective serotonin reuptake inhibitor below 0.15 microM, the effects of the antagonists diverged viz. the 5-HT(1B) receptor antagonist was still able to potentiate citalopram's effect on extracellular 5-HT, while the 5-HT(1A) receptor antagonist was no longer effective. These results suggest that in contrast to 5-HT(1B) autoreceptors, indirect activation of 5-HT(1A) autoreceptors by citalopram is critically related to the dose of selective serotonin reuptake inhibitor administered. The latter may have consequences for selective serotonin reuptake inhibitor augmentation strategies with 5-HT(1A) receptor antagonists in the therapy of depression and anxiety disorders.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Cremers TI,de Boer P,Liao Y,Bosker FJ,den Boer JA,Westerink BH,Wikström HV

doi

10.1016/s0014-2999(00)00247-8

keywords:

subject

Has Abstract

pub_date

2000-05-26 00:00:00

pages

63-74

issue

1

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(00)00247-8

journal_volume

397

pub_type

杂志文章

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