Hyperforin neurotransmitters

Amino acid neurotransmitter Constituents of hypericum also appear to have effects on amino acid neurotransmission, particularly GABA. Hypericin and a crude extract bind to GABAA and GABAB receptors (Cott 1997). Hyperforin also inhibits synaptosomal GABA reuptake in the low micromolar range (IC50 values of 0.05-0.10 ug/ml). Activity at GABAA benzodiazepine receptors was noted in extracts of four hy-... 

Muller WE, Singer A, Wonnemann M, Hafner U, Rolli M, Schafer C. (1998). Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychia y. 31(suppl 1) 16-21. 

The active ingredient of St. John s wort is a substance called hyperforin. Like other antidepressants, hyperforin appears to work by helping to restore the proper balance to brain chemistry. In particular, hyperforin helps restore the balance of certain neurotransmitters, or chemical messengers, in the brain. These neurotransmitters include serotonin, norepinephrine, and dopamine. 

St. John s wort. The St. John s wort plant (Hypericum perforatum Figure 6.4) is an increasingly popular herbal supplement that proponents claim has the ability to cure a vast array of ailments. St. John s wort appears to boost the release of the neurotransmitter serotonin in the brain, which may be the reason it is able to treat anxiety and depression. The herb contains numerous substances, two of which, hypericin and hyperforin, maybe key active ingredients. St. John s wort appears to be effective in relieving the muscle pain associated with fibromyalgia and the tissue pain associated with hemorrhoids. The herb comes in tablet, capsule, cream, and ointment forms and must be taken for several weeks before it takes full effect. St. John s wort should not be taken with antidepressants such as... 

The pharmacological activities of the various constituents of St.John s wort have been studied extensively. Hyperforin appears to be the major bioactive constituent and it acts in several ways serving as a neurotransmitter reuptake inhibitor with a broad selectivity, as a ligand for the pregnane X receptor, and as an antibacterial and antitumor agent. It also has a rapid effect on amyloid precursor protein processing, indicating a possible role in the prevention of Hypericin and the flavonoid constituents may have... 

Assays with extracts devoid of hypericin but with a high content of hyperforin as well as assays with pure hyperforin demonstrated that this metabolite can modulate the function of various neurotransmitters involved in depression, being a potent inhibitor of serotonin, dopamine, noradrenaline and GABA uptake with almost equal potency. Moreover, results from clinical studies evidenced that the antidepressant efficacy of Hypericum preparations correlates with their content of hyperforin [6,87],... 

In a specific work, it has been shown that chemical modification of hyperforin by acylation, oxidation and alkylation produce detrimental effects on the molecule activity as inhibitor of serotonin uptake [89], and the presence of the enolized cyclohexanedione moiety in its structure has been related to its efficacy on the re-uptake of neurotransmitters. 

Thus, pure adhyperforin has been found to have the same inhibitorial potency as hyperforin on the uptake of monoamine neurotransmitters [86], and more polar drug constituents such as flavonoid glycosides and procyanidins [3,87,90] have also been shown to be effective in behavioral models of depression. 

Hyperforin accumulates in translucent glands of leaves of St. John s wort (Soelberg et al., 2007) and represents the major antidepressive principle of this plant. It inhibits the re-uptake of the neurotransmitters serotonin, noradrenaline, dopamine, and GABA, thus increasing their concentrations at the synapses of the brain. This is achieved by an unprecedented mechanism. By elevating the intracellular sodium concentration, hyperforin inhibits the sodium-driven proton gradient required for the transport of neurotransmitters from the synaptic gap into the axoplasm of the neuron (Muller, 2003). 

---