Posted by KaraS on January 6, 2005, at 22:32:08
In reply to Re: St. John's Wort Dopamine » KaraS, posted by Larry Hoover on January 6, 2005, at 11:58:26
> > > St. John's Wort Might Act Via Dopamine Pathway
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> > > NEW YORK (Reuters Health) Dec 27 - The herbal depression remedy St. John's wort (Hypericum perforatum) appears to increase plasma concentration of dihydroxyphenylacetic acid (DOPAC), the main metabolite of dopamine, indicating a novel mode of action, according to German and US researchers.
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> > > In the November issue of Clinical Pharmacology and Therapeutics, Dr. Christoph Schroeder of Medical University Charite, Berlin, and colleagues note that in vitro studies have suggested that the agent's effect may be in part due to inhibition of monoamine transporters and monoamine oxidase.
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> > > To investigate, the researchers randomized 16 healthy subjects to a crossover study of St. John's wort 300 mg three times daily or placebo for 7 days. In addition, seven subjects were randomly assigned to a third study arm in which they were also given the tricyclic antidepressant imipramine for 7 days.
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> > > Compared to placebo, imipramine increased resting blood pressure and heart rate as well as causing a marked orthostatic tachycardia. No such effects were seen with St. John's wort.
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> > > Moreover, St. John's wort had no effect on plasma concentrations of norepinephrine or its main metabolite. However, plasma DOPAC concentrations increased in every subject given the remedy.
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> > > Thus, the researchers conclude that the findings do not support the concept that the agent "elicits a major change in norepinephrine uptake or monoamine oxidase activity."
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> > > The DOPAC effect, they add, may indicate "a heretofore unknown mode of action and should be followed up."
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> >
> > That's fascinating. Thanks for posting this. I had always assumed that SJW was more serotonergic than anything else. I wonder if it could be taken with a noradrenergic to augment it.
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> Actually, SJW disturbs the function of all reuptake pumps, non-selectively.
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> CNS Drug Rev. 2004 Fall;10(3):203-18.
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> Role of hyperforin in the pharmacological activities of St. John's Wort.
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> Zanoli P.
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> Department of Pharmaceutical Sciences, University of Moderna Reggio Emilia, 41100 Modena, Italy. zanoli.paola@unimore.it.
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> The phloroglucinol derivative hyperforin has been recently shown to be a major antidepressant component in the extract of Hypericum perforatum. Experimental studies clearly demonstrated its activity in different behavioral models of depression. Moreover clinical studies linked the therapeutic efficacy of Hypericum extracts to their hyperforin content, in a dose-dependent manner. The molecular mechanism of action of hyperforin is still under investigation. Hyperforin has been shown to inhibit, like conventional antidepressants, the neuronal uptake of serotonin, norepinephrine and dopamine. However, hyperforin inhibits also the uptake of gamma-aminobutyric acid (GABA) and L-glutamate. The uptake inhibition by hyperforin does not involve specific binding sites at the transporter molecules; its mechanism of action seems to be related to sodium conductive pathways, leading to an elevation in intracellular Na(+) concentration. Other additional mechanisms of action of hyperforin, involving ionic conductances as well synaptosomal and vesicular function, have been suggested. In addition to its antidepressant activity, hyperforin has many other pharmacological effects in vivo (anxiolytic-like, cognition-enhancing effects) and in vitro (antioxidant, anticyclooxygenase-1, and anticarcinogenic effects). These effects could be of clinical importance. On the other hand, the role of hyperforin in the pharmacological interactions occurring during Hypericum extract therapy must be fully investigated. Hyperforin seems to be responsible for the induction of liver cytochrome oxidase enzymes and intestinal P-glycoprotein. Several pharmacokinetic studies performed in rats and humans demonstrated oral bioavailability of hyperforin from Hypericum extract. Only recently a new chromatographic method for detection of hyperforin in the brain tissue has been developed and validated. Taking into account the chemical instability of hyperforin, current efforts are directed to the synthesis of new neuroactive derivatives.
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> Lar
>I had previously thought that SJW somehow effected all of those transmitters but doesn't what Iansf just posted about norepinephrine contradict that?:
"Moreover, St. John's wort had no effect on plasma concentrations of norepinephrine or its main metabolite. However, plasma DOPAC concentrations increased in every subject given the remedy.
Thus, the researchers conclude that the findings do not support the concept that the agent "elicits a major change in norepinephrine uptake or monoamine oxidase activity."
The DOPAC effect, they add, may indicate "a heretofore unknown mode of action and should be followed up."
On a personal note, I'm seriously thinking of trying SJW again before I start on an MAOI. I've only tried the Perika version and it made me really sick but I haven't tried HBC or even the Jarrow brand that I have in my cupboard. The Jarrow brand isn't standardized for hyperforin though so may not be a great brand to try. I have taken a capsule of it on a couple of occasions and that didn't make me sick - but I tolerated the rhodiola at first too. If the SJW really is that dopaminergic, then chances are it will make me sick. I have nothing to lose besides a few critical weeks though, right? OTOH, if I can avoid the MAOIs, it might be worth it.
Sorry to go on so about me but this happens to be what I've been pondering all day.Thanks for posting the article, Iansf.
Kara
poster:KaraS
thread:438130
URL: http://www.dr-bob.org/babble/alter/20050101/msgs/438783.html