St. John's Wort Components and the Brain: Uptake, Concentrations Reached and the Mechanisms Underlying Pharmacological Effects

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Abstract:

Hypericum perforatum L. (St. John's wort) extracts have gained popularity as an alternative to conventional antidepressant drugs for mild to moderate forms of depressive disorders. New potential psychiatric uses for extracts in obsessive-compulsive disorder, generalised anxiety disorder and alcohol dependence have also been suggested on the basis of animal studies. The neurochemical mechanisms of these central actions are still debated but several components have antidepressant-like and anxiolytic-like effects in animals, or interact with neurotransmitter systems believed to be causally involved in depression, anxiety and in psychiatric illness generally. However, these data should interpreted taking account of the pharmacokinetic data on the main components, particularly those of their brain distribution and concentrations and the relationships with blood concentrations; the (scant) data so far suggest that the acylphloroglucinol hyperforin, the flavonol quercetin and its glycosylated forms and their metabolites, the biflavones amentoflavone and its I3,II8-analog biapigenin and the naphthodianthrones hypericin and pseudohypericin pass the blood-brain barrier poorly in animals. The brain concentrations of all these high-molecular weight, poorly water-soluble compounds after pharmacologically effective doses of the extracts are therefore far below those effective on neurotransmitter receptors and the mechanisms which are obviously important in the central effects of conventional, pharmacologically related drugs. Additional pharmacokinetic data on the brain concentrations of these and other constituents and their metabolites are therefore required for a more meaningful interpretation of the central effects of St. John's Wort extracts.





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  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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