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, β-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 C 6-cell cultures to Ze 117 extract resulted in a dose-dependent
β-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.
References
Mechanisms of action of antidepressant treatments: implications for the etiology and
treatment of depressive disorders. In Meltzer, H.Y. (ed.) Psychopharmacology: The third generation of progress. New
York, Raven Press 1987: 535-544
