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 pK i values of 8.41 ± 0.12 and 7.43 ± 0.06 respectively. The 5-HT 3/5-HT 4 receptor antagonist tropisetron and the 5-HT 1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) had similar inhibitory potencies to cocaine (pK i 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 pK i 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.