Panuramine, a selective inhibitor of uptake of 5-hydroxytryptamine in the brain of the rat.

The neurochemical profile of the novel inhibitor of uptake of 5-hydroxytryptamine (5-HT) panuramine (Wy 26002) has been investigated in the rat. In vitro, panuramine was found to be a potent and selective inhibitor of uptake of 5-HT with an IC50 of 22 +/- 4 nM. The IC50 for inhibition of uptake of noradrenaline was 848 nM and that for uptake of dopamine greater than 10 micron. Panuramine, in concentrations up to 10 micron did not displace the specific binding of either [3H]spiroperidol or [3H]5-HT and had no effect on the spontaneous or potassium-evoked release of 5-HT, suggesting that the compound had little effect on serotonergic transmission other than the inhibition of uptake of 5-HT. Panuramine also produced a dose-related antagonism of the depletion of 5-HT in brain induced by p-chloroamphetamine, confirming the ability of the drug to inhibit uptake of 5-HT in vivo.