Inhibition of 5-ht Uptake by Some Constituents of Hypericum Annulatum in Rat Brain in Vitro

Hyperatomarin, annulatophenone and gentisein are constituents of Hypericum annulatum Moris – a perennial herb, indigenous to the Balkan Peninsula and Sardinia. The aim of the study was to investigate the effects of these compounds at serotonin binding and uptake in rat brain sinaptosomes. Radioligand techniques with [H]-5HT were used in order to determine a profile of pharmacological activity in vitro. All tested compounds inhibit serotonin uptake in micromolar concentrations. Gentisein showed the most potent serotonin uptake inhibition with an IC50 value of 4.7 μM. Annulatophenone inhibits serotonin uptake with IC50 value of 5.4 μM, while hyperatomarin inhibition is the weakest IC50 16.8 μM. Our observations suggest that the mechanism of action of the Hypericum constituents is probably not associated with a specific binding to 5-HT1B receptors, but might be related to the inhibition of serotonine uptake. This effect is probably not caused by a direct effect of the derivatives on 5-HT1B sites.