The effect of 5-HT receptor ligands on the uptake of [3H]5-hydroxytryptamine into rat cortical synaptosomes.

The effect of 5-HT receptor agonists and antagonists to inhibit [3H]5-HT uptake was investigated in rat cortical synaptosomes. The 5-HT (5-hydroxytryptamine) uptake inhibitors paroxetine and fluoxetine yielded pKi values of 8.41 +/- 0.12 and 7.43 +/- 0.06 respectively. The 5-HT3/5-HT4 receptor antagonist tropisetron and the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) had similar inhibitory potencies to cocaine (pKi values of 6.58 +/- 0.04, 6.47 +/- 0.14 and 6.45 +/- 0.12 respectively). The dopamine and noradrenaline uptake inhibitors GBR12909 and desipramine had comparable values of 6.5 +/- 0.05 and 6.13 +/- 0.07. Other 5-HT receptor ligands had pKi values less than 6.0 (R(+)-zacopride, MDL72222, R(+)/S(-)-zacopride) or 5.0 (5-methoxytryptamine, m-chlorophenylbiguanide, S(-)-zacopride, SDZ205-557, ondansetron and renzapride). It is concluded, with the possible exception of tropisetron and 8-OH-DPAT, that it is unlikely that the effects of the 5-HT receptor ligands to inhibit 5-HT uptake contribute to their effects in vivo.