Hypericum perforatum L. (St John's wort) extract Ze 117 inhibits dopamine re-uptake in rat striatal brain slices. An implication for use in smoking cessation treatment?

Classic synthetic antidepressant drugs, as well as St John's wort extract (SJW), directly inhibit the re-uptake of norepinephrine (NE) and/or serotonin (5-HT) into pre-synaptic axons. With chronic treatment they induce adaptive changes in a number of neurotransmitter receptors in synaptic membranes. The immediate effects of SJW Ze 117, an extract low in hyperforin content, on the specific dopamine (DA) uptake were studied in rat striatal brain slices and compared with the effects on NE and 5-HT uptake in rat cortical brain slices. Specific DA uptake was inhibited in a dose dependent manner. In contrast to the findings in synaptosomal preparations published so far, the extract showed different inhibitory potencies for the respective transporters. The potencies for the uptake inhibition of NA, DA and 5-HT were 30, 7 and 1, respectively. The results indicate that the SJW Ze 117 extract interferes in three ways with the individual uptakes of the relevant neurotransmitters that are considered to be causal in the development of depression. This observation, the concomitant and potent inhibition of DA re-uptake by SJW extract, may additionally provide a rationale for the treatment of nicotine or drug addiction with SJW.

St. John's wort extract Ze 117 (Hypericum perforatum) inhibits norepinephrine and serotonin uptake into rat brain slices and reduces 3-adrenoceptor numbers on cultured rat brain cells.

Despite almost forty years of widespread use, the mode of action of antidepressant drugs is still largely unknown. There is agreement that these drugs interact with central neurotransmission. Common findings are acute inhibitory actions on reuptake mechanisms for norepinephrine (NE) and for serotonin (5-HT) at presynaptic axons and chronic adaptive effects on neurotransmitter receptors on postsynaptic membranes. In particular, beta-adrenoceptor downregulation has been observed after chronic treatment with most antidepressants in vivo and in cell culture systems. We studied the effectiveness of Ze 117 (St. John's wort) extract (Hypericum perforatum) on NE- and 5-HT-uptake into rat brain slices. Potency and efficacy of the Ze 117 extract were compared with those of tricyclic (TCA) and selective serotonin reuptake inhibitor (SSRI)-type antidepressants. A dose-dependent inhibition was seen on NE and 5-HT uptake into brain slices. The Ze 117 extract was more selective for the uptake of NE than for that of 5-HT. The maximal extent of uptake inhibition by Ze 117 extract was comparable to that of imipramine (IMI), desipramine (DMI) or fluvoxamine for 5-HT, but lower for NE transport, than that of the synthetic antidepressants. Chronic exposure (8 days) of confluent C6-cell cultures to Ze 117 extract resulted in a dose-dependent beta-adrenoceptor downregulation equal to that induced by DMI, a potent TCA. None of these effects could be achieved with either hypericin or hyperforin alone in a relevant dose range. Our results indicate that the St. John's wort extract Ze 117 contains active, but as yet unknown antidepressant principles with effects comparable to those of TCAs.