Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 345, Issue 2, pp 129–136

Evidence for various tryptamines and related compounds acting as substrates of the platelet 5-hydroxytryptamine transporter

  • Reinhard Wölfel
  • Karl-Heinz Graefe
Article

DOI: 10.1007/BF00165727

Cite this article as:
Wölfel, R. & Graefe, KH. Naunyn-Schmiedeberg's Arch Pharmacol (1992) 345: 129. doi:10.1007/BF00165727

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.

Key words

Rabbit platelets 5-HT transporter Carrier-mediated efflux Tryptamines 5-HT receptor agonists 

Abbreviations

MAO

monoamine oxidase

5-HT

5-hydroxytryptamine

2-M-5-HT

2-methyl-5-HT

N-M-5-HT

ωN-methyl-5-HT

N,N-DM-5-HT

N,N-dimethyl-5-HT

S(+)α-M-5-HT

S(+)α-methyl-5-HT

5-CT

5-carboxamidotryptamine

5-M-tryptamine

5-methyltryptamine

5-MO-tryptamine

5-methoxytryptamine

7-M-tryptamine

7-methyltryptamine

N-M-tryptamine

ωN-methyltryptamine

N,N-DM-tryptamine

N,N-dimethyltryptamine

N,N-DM-5-MO-tryptamine

N,N-dimethyl-5-methoxytryptamine

(±)8-OH-DPAT

(±)8-hydroxy-2-2-(N,N-dipropylamino)tetralin

5-M-urapidil

5-methyl-urapidil

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Reinhard Wölfel
    • 1
  • Karl-Heinz Graefe
    • 1
  1. 1.Institut für Pharmakologie und Toxikologie der Universität WürzburgWürzburgFederal Republic of Germany

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