Potential antidepressant properties of IDN 5491 (hyperforin-trimethoxybenzoate), a semisynthetic ester of hyperforin

Cervo, Luigi; Mennini, Tiziana; Rozio, Marco; Ekalle-Soppo, Charlotte Blanche; Canetta, Alessandro; Burbassi, Silvia; Guiso, Giovanna; Pirona, Lorenza; Riva, Antonella; Morazzoni, Paolo; Caccia, Silvio; Gobbi, Marco

doi:10.1016/j.euroneuro.2004.07.004

Cited by 16 publications

(16 citation statements)

References 42 publications

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“…The antidepressant-like activity of hyperforin trimethoxybenzoate was completely antagonized by pre-treating rats with BD 1047, a selective sigma 1 antagonist (Cervo et al, 2004). These results, together with the observation that agonists at sigma 1 receptors are active in antidepressant models in rats (Matsuno et al, 1996), suggest that the SJW extract's antidepressant effect might be mediated by an indirect action on sigma receptors (i.e.…”

Section: Sigma Receptorsmentioning

confidence: 69%

“…Moreover, haloperidol (D 2 /D 4 and sigma receptor antagonist) and sulpiride (selective D 2 /D 3 receptor antagonist) completely antagonized the effects of the extract in the ''forced swimming test'' in rats . Sulpiride also antagonised the anti-immobility effect of solubilized hypericin (Butterweck et al, 1998) and hyperforin trimethoxybenzoate (Cervo et al, 2004). This suggests that D 2 receptors are involved in SJW's effect on immobility, although it or its components do not bind to D 2 receptors in vitro.…”

Section: Serotoninergic Systemmentioning

confidence: 85%

“…In spite of the lack of affinity in vitro, it was recently reported that pre-treatment of rats with pharmacologically active doses of SJW extracts or hyperforin trimethoxybenzoate reduced ligand binding to sigma receptors, measured ex vivo (Pirona et al, 2002, Cervo et al, 2004. The antidepressant-like activity of hyperforin trimethoxybenzoate was completely antagonized by pre-treating rats with BD 1047, a selective sigma 1 antagonist (Cervo et al, 2004).…”

Section: Sigma Receptorsmentioning

confidence: 94%

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The antidepressant mechanism of Hypericum perforatum

2004

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Section: Sigma Receptorsmentioning

confidence: 69%

Section: Serotoninergic Systemmentioning

confidence: 85%

Section: Sigma Receptorsmentioning

confidence: 94%

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The antidepressant mechanism of Hypericum perforatum

2004

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“…However, the poor stability of hyperforin when extracted from the herb and exposed to light and air, and its ease to oxidation certainly complicates the preparation of pharmaceutical and nutritional formulations of Hypericum perforatum whose pharmacological activities may be rapidly lost during storage [48]. This has led to the synthesis of more stable analogues, including esters and reduced derivatives of hyperforin which have undergone preliminary preclinical evaluation as potential antidepressants [49][50][51].…”

Section: Antidepressant-like Componentsmentioning

confidence: 98%

Antidepressant-Like Components of Hypericum perforatum Extracts: An Overview of Their Pharmacokinetics and Metabolism

Caccia

2005

CDM

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Extracts of Hypericum perforatum are becoming increasingly popular for the treatment of mild to moderate depression, despite the lack of consensus on their efficacy. Although the mechanism(s) of this action are still debated, several components, including the naphthodianthrones hypericin and pseudohypericin, the acylphloroglucinol hyperforin and some flavonols, are believed to play major roles in the antidepressant-like effects. Some of these also increase the expression of the P-glycoprotein transporter and others the expression of cytochrome P450 enzymes, possibly contributing to the interactions involving the extracts and conventional drugs. However, few pharmacokinetic studies of naphthodianthrones and hyperforin have appeared and none has yet evaluated the exposure to unchanged quercetin and its glycosides after intake of extracts. There are no formal pharmacokinetic studies in special populations. Bioavailability appears low, giving variable steady-state plasma concentrations, whose prediction may be complicated by non-linearity for hypericin and hyperforin. Data on tissue distribution are scarce, and it appears that hypericin and hyperforin do not reach the central nervous system in appreciable concentrations in animals. Clearance is low-intermediate, with little or no unchanged compounds excreted with urine. Although some potentially active conjugated metabolites have been identified for quercetin and its glycosides after intake of authentic compounds or flavonol-rich foods, these too have been characterised little with regard to their pharmacokinetics and central activities. Thus, further pharmacokinetic and pharmacodynamic studies of the main components and their metabolites are urgently needed to clarify the role of each constituent and provide more rational and safe regimens for people preferring "natural" drugs.

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“…In spite of the lack of affinities of hypericin/hyperforin for sigma receptors in vitro, pretreatment of rats with pharmacologically active doses of SJW extracts reduced ligand binding to sigma receptors, measured ex vivo [48,49]. Consistent with this possibility is the finding that rimcazole (a sigma 1 receptor antagonist) counteracts the antidepressant effects of the SJW extract, evaluated with the forced swimming test in rats [8], and that agonists at sigma 1 receptors are active in antidepressant models in rats [50].…”

Section: Discussionmentioning

confidence: 99%

Potential antidepressant properties of IDN 5491 (hyperforin-trimethoxybenzoate), a semisynthetic ester of hyperforin

Cited by 16 publications

References 42 publications

The antidepressant mechanism of Hypericum perforatum

The antidepressant mechanism of Hypericum perforatum

Antidepressant-Like Components of Hypericum perforatum Extracts: An Overview of Their Pharmacokinetics and Metabolism

St. John’s Wort and its active principles in depression and anxiety — A critical analysis of receptor binding studies

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