caa a22 4500 469079827 CHVBK 20180323132946.0 cr unu---uuuuu 170328e19920201xx s 000 0 eng 10.1007/BF00165727 doi (NATIONALLICENCE)springer-10.1007/BF00165727 Evidence for various tryptamines and related compounds acting as substrates of the platelet 5-hydroxytryptamine transporter [Elektronische Daten] [Reinhard Wölfel, Karl-Heinz Graefe] Summary: The aim of the present study was to answer the question whether amines other than 5-hydroxytryptamine (5-HT) and tryptamine act as substrates of the platelet 5-HT transporter. To this end, a large number of tryptamines, 5-HT receptor agonists and phenethylamines (which had IC50 values for 3H-5-HT uptake inhibition of 145-24500 nmol l−1) was examined in rabbit platelets in order to determine their ability to induce an outward transport of 3H-5-HT Platelets (the MAO of which was blocked) from reserpine-pretreated animals were loaded with 3H-5-HT and then exposed for 5 min to various concentrations (ranging from 0.25 to 40 times the IC50) of each compound. The concentration-effect curves for the drug-induced increase in 3H-5-HT efflux served to determine values of Emax (maximum increase in efflux expressed in % of the 3H-5-HT content of cells) and EC50 (drug concentration producing Emax/2). For the 24 compounds studied here (which included the 5-HT uptake inhibitors imipramine, citalopram, fluoxetine and cocaine) a linear correlation between EC50 and IC50 (r = 0.975) and a mean ratio of EC50/IC50 of 2.4 was found. Most of the compounds [e.g., (±)8-hy-ydroxy-2-(N,N-dipropylamino)tetralin, S(+)α-methyl-5-HT, 5-carboxamidotryptamine and 5-methoxytryptamine] gave rise to Emax values (15.8-32.5%) that exceeded that brought about by imipramine (6.6%), indicating that they act as substrates of the 5-HT transporter; the 3H-5-HT outward transport observed in response to these substances was abolished in the presence of imipramine. Others (e.g., 2-methyl-5-HT and 5-methylurapidil) produced Emax values (3.4-14.3%) not significantly different from that of imipramine and, therefore, can be classified either as poor substrates or as inhibitors of the 5-HT transporter. Hence, many tryptamines and 5-HT receptor agonists are substrates of the platelet 5-HT transporter. The property of being substrates gives them the latent capacity to bring about release of endogenous 5-HT and, as a result, to cause indirect 5-HT receptor-mediated effects. Springer-Verlag, 1992 Rabbit platelets nationallicence 5-HT transporter nationallicence Carrier-mediated efflux nationallicence Tryptamines nationallicence 5-HT receptor agonists nationallicence MAO : monoamine oxidase nationallicence 5-HT : 5-hydroxytryptamine nationallicence 2-M-5-HT : 2-methyl-5-HT nationallicence N-M-5-HT : ωN-methyl-5-HT nationallicence N,N-DM-5-HT : N,N-dimethyl-5-HT nationallicence S(+)α-M-5-HT : S(+)α-methyl-5-HT nationallicence 5-CT : 5-carboxamidotryptamine nationallicence 5-M-tryptamine : 5-methyltryptamine nationallicence 5-MO-tryptamine : 5-methoxytryptamine nationallicence 7-M-tryptamine : 7-methyltryptamine nationallicence N-M-tryptamine : ωN-methyltryptamine nationallicence N,N-DM-tryptamine : N,N-dimethyltryptamine nationallicence N,N-DM-5-MO-tryptamine : N,N-dimethyl-5-methoxytryptamine nationallicence (±)8-OH-DPAT : (±)8-hydroxy-2-2-(N,N-dipropylamino)tetralin nationallicence 5-M-urapidil : 5-methyl-urapidil nationallicence Wölfel Reinhard Institut für Pharmakologie und Toxikologie der Universität Würzburg, Versbacher Straße 9, W-8700, Würzburg, Federal Republic of Germany aut Graefe Karl-Heinz Institut für Pharmakologie und Toxikologie der Universität Würzburg, Versbacher Straße 9, W-8700, Würzburg, Federal Republic of Germany aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/2(1992-02-01), 129-136 0028-1298 345:2<129 1992 345 210 https://doi.org/10.1007/BF00165727 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00165727 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wölfel Reinhard Institut für Pharmakologie und Toxikologie der Universität Würzburg, Versbacher Straße 9, W-8700, Würzburg, Federal Republic of Germany aut NATIONALLICENCE 700 1- Graefe Karl-Heinz Institut für Pharmakologie und Toxikologie der Universität Würzburg, Versbacher Straße 9, W-8700, Würzburg, Federal Republic of Germany aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/2(1992-02-01), 129-136 0028-1298 345:2<129 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer