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Effects of monoamine uptake inhibitors on extracellular and platelet 5-hydroxytryptamine in rat blood: different effects of clomipramine and fluoxetine

AuthorsOrtiz, Jordi; Fabrias, Francesc
Keywords5-hydroxytryptamine uptake
Antidepressant drugs
Uptake inhibitors
Endothelial uptake
Issue DateApr-1992
PublisherNational Institutes of Health (U.S.). PubMed Central
CitationBritish Journal of Pharmacology 105(4): 941–946 (1992)
AbstractThe concentration of 5-hydroxytryptamine (5-HT) in rat platelet-free plasma increased significantly 30 min after a single i.p. injection (10 mg kg-1) of each of six inhibitors of the high-affinity 5-HT uptake (fluvoxamine, fluoxetine, alaproclate, paroxetine, sertraline and clomipramine). The increases ranged from 226% to 776% of control values. In contrast, imipramine, desipramine and femoxetine had no significant effect. The increase elicited by paroxetine was dependent on the dose (1, 5 and 10 mg kg-1) and returned to control values after 4 h. That observed after clomipramine was also transient and paralleled the plasma concentration of the drug (Spearman-rank correlation r = 0.43).
In vivo, the rat pulmonary vascular endothelium removed trace amounts (8.8 nmol in a bolus) of intravenously injected [14C]-5-HT. Paroxetine pretreatment (10 mg kg-1, 30 min before-hand) reduced this uptake by 73%.
Repeated fluoxetine treatments reduced rat whole blood 5-HT concentration (ca. -60% after daily 2 x 5 mg kg-1, i.p. during 14 days). However, plasma (extracellular) 5-HT was not increased.
Various repeated treatments with clomipramine (i.p. injections or osmotic minipumps, up to 30 mg kg-1 day-1), failed to decrease rat whole blood 5-HT concentrations. Platelet-free plasma 5-HT was also unchanged, even after treatments yielding plasma clomipramine levels 2.7 times higher than those that increased it acutely.
These results indicate that the extracellular pool of 5-HT in rat blood (measured in the platelet-free plasma) is physiologically under the control of high-affinity 5-HT uptake systems.
Description6 pages, 5 figures, 1 table.-- PMID: 1387022 [PubMed].-- PMCID: PMC1908726.
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