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Hyperforin activates nonselective cation channels – A new mechanism of antidepressant activity
The preclinical antidepressant profile of hyperforin is supported by a large body of evidence. Hyperforin inhibits the synaptosomal uptake of several neurotransmitters in vitro. However, the mechanism of uptake inhibition is different from other antidepressants. Since similar concentrations of hyperforin inhibit the serotonin uptake and elevate the [Na+]i, concentration, we suggested that serotonin uptake inhibition might be the consequence of the elevation of [Na+]i, as the uptake of neurotransmitters is depending on the sodium gradient. Beside other pathways Na+ entry into cells is mediated by nonselective cation channels (NSCC) which can be blocked by SK&F 96365 and LOE 908. SK&F 96365 completely blocked the hyperforin-induced influx of Na+ into platelets and dissociated mouse brain cells and LOE 908 was also active. These findings indicate that NSCC are involved in the hyperforin-induced influx of Na+. Therefore we propose activation of nonselective cation channels as a novel mechanism of antidepressant activity.