Hyperforin--antidepressant activity by a novel mechanism of action.
Hyperforin represents a major antidepressive constituent of St. John's wort (SJW) extract. It not only inhibits the neuronal uptake of serotonin, norepinephrine and dopamine like many other antidepressants, but also inhibits GABA and L-glutamate uptake. This broad-spectrum effect is obtained by an elevation of the intracellular Na+ concentration, probably due to activation of sodium conductive pathways not yet finally identified but most likely ionic channels. This makes hyperforin the first member of a new class of compounds with a preclinical antidepressant profile due to a completely novel mechanism of action.
Müller
W E
WE
Department of Pharmacology, University of Frankfurt, Frankfurt/M., Germany.
Singer
A
A
Wonnemann
M
M
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D001643:Bridged Bicyclo Compounds; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D020902:Hypericum; D051379:Mice; D010696:Phloroglucinol / Q000031:analogs & derivatives; D010936:Plant Extracts / Q000494:pharmacology*; D012701:Serotonin / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D014316:Tritium
D000928:Antidepressive Agents; D001643:Bridged Bicyclo Compounds; D010936:Plant Extracts; D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers; D013729:Terpenes; D014316:Tritium; D012701:Serotonin; D012964:Sodium; D010696:Phloroglucinol; C001654:hyperforin