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• W2023596960 abstract "On the basis of preclinical data, the suggestion of a ‘Prozac®-like’ mechanism of action is still highly speculative. Furthermore, clinical studies indicate that St John's wort differs from monoamine uptake inhibitor antidepressants in its therapeutic indications: ‘mild-to-moderate’ 11xSt. John's wort for depression – an overview and meta-analysis of randomised clinical trials. Linde, K. et al. Br. Med. J. 1996; 313: 253–258Crossref | PubMedSee all References11, but not major, depression 12xEffectiveness of St John's Wort in major depression. Shelton, R.C. et al. J. Am. Med. Assoc. 2001; 285: 1978–1986CrossrefSee all References12. Finally, its better safety profile 11xSt. John's wort for depression – an overview and meta-analysis of randomised clinical trials. Linde, K. et al. Br. Med. J. 1996; 313: 253–258Crossref | PubMedSee all References, 13xSafety of Hypericum in patients with depression. Stevinson, C. and Ernst, E. CNS Drugs. 1999; 11: 125–132CrossrefSee all References is difficult to reconcile with the plethora of effects induced in vitro by similar hyperforin concentrations: in addition to altering ionic homeostasis in nerve endings, hyperforin also influences various neuronal ionic conductances 14xHyperforin attenuates various ionic conductance mechanisms in the isolated hippocampal neurons of rat. Chatterjee, S. et al. Life Sci. 1999; 65: 2395–2405Crossref | PubMed | Scopus (48)See all References14 and interacts with opioid receptors 15xExtracts and constituents of Hypericum perforatum inhibit the binding of various ligands to recombinant receptors expressed with the Semliki forest virus system. Simmen, U. et al. J. Recept. Signal Transduction Res. 1999; 19: 59–74Crossref | PubMedSee all References15.The mechanism of action of St John's wort extracts might therefore be different from that of conventional antidepressants (i.e. it might not act directly on monoaminergic nerve terminals, although the final target of synthetic and herbal antidepressant drugs should be the facilitation of monoaminergic transmission, whatever the mechanism of action). Thus, it would be important to consider and investigate mechanisms of St John's wort activity other than the direct effect on monoamine uptake. To date, binding studies have not identified any receptor to which constituents of St John's wort extracts bind with sufficiently high affinity 6xIn vitro binding studies with two Hypericum perforatum extracts, hyperforin, hypericin and biapigenin on 5-HT6, 5-HT7, GABAA/benzodiazepine, sigma, NPY–Y1 /Y2 receptors and dopamine transporters. Gobbi, M. et al. Pharmacopsychiatry. 2001; 34: S45–S48Crossref | PubMedSee all References, 15xExtracts and constituents of Hypericum perforatum inhibit the binding of various ligands to recombinant receptors expressed with the Semliki forest virus system. Simmen, U. et al. J. Recept. Signal Transduction Res. 1999; 19: 59–74Crossref | PubMedSee all References, 16xIn vitro receptor binding and enzyme inhibition by Hypericum perforatum extract. Cott, J.M. Pharmacopsychiatry. 1997; 30: 108–112Crossref | PubMedSee all References. However, the in vitro affinities reported for many relevant CNS receptors 16xIn vitro receptor binding and enzyme inhibition by Hypericum perforatum extract. Cott, J.M. Pharmacopsychiatry. 1997; 30: 108–112Crossref | PubMedSee all References16 need to be reconfirmed and completed, although to interpret the in vitro data correctly we also need to know the brain concentrations of the main constituents (not only hyperforin) after systemic treatment with St John's wort extract. Finally, the possibility that active metabolites are formed in vivo and bind with high affinity to CNS receptors relevant to the antidepressant activity of St John's wort should be considered." @default.
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• W2023596960 title "Is St John's wort a ‘Prozac-like’ herbal antidepressant?" @default.
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