Plasma free 5-hydroxytryptamine (5-HT): Evidence of an increase induced by LM 5008, a potent 5-HT uptake inhibitor
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AbstractWhen 5-HT platelet uptake was inhibited in rats by single or repeated oral administration of 4-[2-(3-indolyl)ethyl]piperidine (LM 5008), 5-hydroxy-indole-acetic acid (5-HIAA) and 5-HT platelet concentration decreased. An oral administration of LM 5008 (10 mg/kg) to rats whose platelets were previously labeled with tritiated 5-HT provoked an increase in plasma free 5-HT and 5-HIAA. The maximum rise in 5-HT occured at 15 min while that of 5-HIAA appeared later (30 min). Concurrently urinary excretion of 5-HT was dramatically increased (about 5 times the control value) which indicates that 5-HT metabolism was not stimulated. According to the similarity between blood platelets and tryptaminergic neurons, plasma free 5-HT variations appeat to reflect changes of the neurotransmitter level into the synaptic cleft. Moreover, the excess of plasma free 5-HT induced by LM 5008 could improve 5-HT effects on vascular tone and pain.

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