![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 18 of 18. This is the beginning of the thread.
Posted by qqqsimmons on November 2, 2006, at 10:09:04
front page article in the paper today on resveratrol: http://www.suntimes.com/lifestyles/121132,CST-NWS-fat02.article)
what they don't tell you is that resveratrol, like its cousin quercetin, is a MAO inhibitor and may cause mania (or relieve clinical depression if you got it). i've already experienced the insomnia with quercetin...i wonder if you combine taurine with these, would it counter the overstimulating side effects???
Inhibitory effects of cis- and trans-resveratrol on noradrenaline and 5-hydroxytryptamine uptake and on monoamine oxidase activity.
Yanez M, Fraiz N, Cano E, Orallo F.
Departamento de Farmacologia, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela (La Coruna), Spain.This study investigated for the first time the potential effects of cis- and trans-resveratrol (c-RESV and t-RESV) on noradrenaline (NA) and 5-hydroxytryptamine (5-HT) uptake by synaptosomes from rat brain, on 5-HT uptake by human platelets, and on monoamine oxidase (MAO) isoform activity. Both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the uptake of [3H]NA and [3H]5-HT by synaptosomes from rat brain and the uptake of [3H]5-HT by human platelets. In both experimental models, t-RESV was slightly more efficient than c-RESV. Furthermore, in synaptosomes from rat brain, the RESV isomers were less selective against [3H]5-HT uptake than the reference drug fluoxetine (0.1-30 microM). On the other hand, both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the enzymatic activity of commercial (human recombinant) MAO isoform (MAO-A and MAO-B) activity, c-RESV being slightly less effective than t-RESV. In addition, both RESV isomers were slight but significantly more selective against MAO-A than against MAO-B. Since the principal groups of drugs used in the treatment of depressive disorders are NA/5-HT uptake or MAO inhibitors, under the assumption that the RESV isomers exhibit a similar behaviour in humans in vivo, our results suggest that these natural polyphenols may be of value as structural templates for the design and development of new antidepressant drugs with two important biochemical activities combined in the same chemical structure: NA/5-HT uptake and MAO inhibitory activity.
Posted by linkadge on November 2, 2006, at 10:58:35
In reply to resveratrol improves lifespan, makes you manic?, posted by qqqsimmons on November 2, 2006, at 10:09:04
I find it all very interesting.
I don't know if quercetin has effects on monoamine uptake, but I do know it has effects on MAO-A, and COMT. Quercetin and resveratrol are often found together, in which case one would be getting COMT, MAO, and uptake inhibition.
Interesting that one compound displays both serotonin uptake inhibition and MAO activity.
I found resveratrol to be a very effective antidepressant. If only it were synthesized and made available in a more standardized form.
Linkadge
Posted by nolvas on November 2, 2006, at 11:08:32
In reply to Re: resveratrol improves lifespan, makes you manic?, posted by linkadge on November 2, 2006, at 10:58:35
This supplement looks interesting. Not sure how much Reservatrol is required. I will have to look at the studies.
Posted by TENMAN on November 2, 2006, at 11:18:42
In reply to Re: resveratrol improves lifespan, makes you manic?, posted by linkadge on November 2, 2006, at 10:58:35
> I find it all very interesting.
>
> I don't know if quercetin has effects on monoamine uptake, but I do know it has effects on MAO-A, and COMT. Quercetin and resveratrol are often found together, in which case one would be getting COMT, MAO, and uptake inhibition.
>
> Interesting that one compound displays both serotonin uptake inhibition and MAO activity.
>
> I found resveratrol to be a very effective antidepressant. If only it were synthesized and made available in a more standardized form.
>
> Linkadge
>
>
>
Posted by qqqsimmons on November 2, 2006, at 11:30:09
In reply to Re: resveratrol improves lifespan, makes you manic?, posted by linkadge on November 2, 2006, at 10:58:35
yeah, i guess the EGCG in green tea is a COMT inhibitor too.
i read on pubmed where some mother was giving quercetin to her 22-month-old. the doctor was banging his head trying to figure out why the kid was peeing out so much homovanillic acid (a dopamine metabolite), thought the kid had a tumor or something.
i wonder if these COMT/MAO inhibitory effects might contribute to the health benefits of quercetin, resveratrol and green tea's egcg.
i'd like to have a quick way to clear the norepinephrine out of my system, so i could sleep, put on weight, etc. but i haven't found anyway to boost COMT or MAO. though i've heard that lithium may work by helping eliminate dopamine??? but i don't think it's recommended to take lithium without doctor's supervision, which is a bummer.
well, maybe we can just get used to three, four, five hours sleep a night.
i read (http://en.wikipedia.org/wiki/Monoamine_oxidase) that people have different MAO genes and so break transmitters down at different rates. i expect that norepinephrine stays in my system longer than most. often i can't relax.
> I find it all very interesting.
>
> I don't know if quercetin has effects on monoamine uptake, but I do know it has effects on MAO-A, and COMT. Quercetin and resveratrol are often found together, in which case one would be getting COMT, MAO, and uptake inhibition.
>
> Interesting that one compound displays both serotonin uptake inhibition and MAO activity.
>
> I found resveratrol to be a very effective antidepressant. If only it were synthesized and made available in a more standardized form.
>
> Linkadge
>
>
>
Posted by linkadge on November 2, 2006, at 11:37:48
In reply to Re: resveratrol improves lifespan, makes you manic?, posted by qqqsimmons on November 2, 2006, at 11:30:09
I've heard that low MAO genes are related to persistance - If too low, agression, impulsivity, antisocial behavior.
Low COMT is related to certain disorders like ultra-rapid cycling bipolar, but also linked to better executive function and less panic disorder. Though, Its all uncertain in my opinion.
Linkadge
Posted by nolvas on November 2, 2006, at 16:30:30
In reply to Re: resveratrol improves lifespan, makes you manic?, posted by linkadge on November 2, 2006, at 11:37:48
Some COMT information regarding Bipolar with and without panic disoder.
Posted by nolvas on November 2, 2006, at 16:39:08
In reply to Re: resveratrol improves lifespan, makes you manic, posted by nolvas on November 2, 2006, at 16:30:30
Some more info on COMT >
Catechol-O-Methyltransferase is a type of (endogenous) Transmethylase Transferase Enzyme. It is present in most body tissues.
Biological Function of COMT >Nervous System
COMT catalyzes the metabolism of various Catecholamines to their metabolic products for excretion via the Urine:
- Caution: excessive metabolism of Catecholamines by COMT can cause the depletion of Catecholamines.
- COMT catalyzes the conversion of Adrenaline to Metanephrine.
- COMT catalyzes the conversion of Dopamine to 3-Methoxytyramine.- COMT catalyzes the conversion of Norepinephrine to Normetanephrine.
These Substances may Enhance the Function of COMT >Amino Acids
S-Adenosylmethionine (SAMe) is a cofactor for COMT.
Minerals
Magnesium is a cofactor for COMT. < hmm that's interesting
These Substances may Inhibit the Excessive Activity of COMT >
Polyphenols
Quercetin may inhibit COMT.
These Herbs may Inhibit the Excessive Activity COMT >
Green Tea may inhibit COMT (due to the Tea Polyphenols content of Green Tea).
Saint John’s Wort may inhibit the excessive destruction of Catecholamines by COMT.
Siberian Ginseng may inhibit COMT.
Posted by linkadge on November 2, 2006, at 19:22:41
In reply to Re: resveratrol improves lifespan, makes you manic, posted by nolvas on November 2, 2006, at 16:39:08
Hmm. Too bad they didn't describe what varients of the COMT gene were involved.
Panic disorder for instance, could result from excessive or deficiant catecholamine levels.
Yeah, that is interesting that magnesium affects COMT in such a way. I wonder if that is a mechanism by which it helps some anxiety, via lowering of catecholamines.
Linkadge
Posted by linkadge on November 2, 2006, at 19:24:18
In reply to Re: resveratrol improves lifespan, makes you manic, posted by nolvas on November 2, 2006, at 16:39:08
I wonder the feel of a pure COMT inhibitor? Green tea might be close, but green tea also acts as an acetycholinsterase inhibitor. It also contains theanine etc.
Linkadge
Posted by linkadge on November 2, 2006, at 19:40:15
In reply to Re: resveratrol improves lifespan, makes you manic, posted by linkadge on November 2, 2006, at 19:24:18
Actually, I am interested in compounds that could increase monoamine oxidase activity.
Linkadge
Posted by qqqsimmons on November 4, 2006, at 9:16:57
In reply to Re: resveratrol improves lifespan, makes you manic, posted by linkadge on November 2, 2006, at 19:24:18
what does acetycholinsterase inhibition do?
green tea is also a goitrogen, meaning it suppresses thyroid hormone release, so it appears that green tea slows you down while it speeds you up with comt inhibition, not to mention the caffeine.
these herbs are too damn complicated.
> I wonder the feel of a pure COMT inhibitor? Green tea might be close, but green tea also acts as an acetycholinsterase inhibitor. It also contains theanine etc.
>
> Linkadge
Posted by qqqsimmons on November 4, 2006, at 9:55:34
In reply to Re: resveratrol improves lifespan, makes you manic, posted by nolvas on November 2, 2006, at 16:39:08
thanks for the info on SAMe and Mg.
i had to find the details:
COMT
FUNCTION: Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
CATALYTIC ACTIVITY: S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol.
COFACTOR: Magnesium.
> These Substances may Enhance the Function of COMT >
>
> Amino Acids
>
> S-Adenosylmethionine (SAMe) is a cofactor for COMT.
>
> Minerals
>
> Magnesium is a cofactor for COMT. < hmm that's interesting
>
> These Substances may Inhibit the Excessive Activity of COMT >
>
> Polyphenols
>
> Quercetin may inhibit COMT.
>
> These Herbs may Inhibit the Excessive Activity COMT >
>
> Green Tea may inhibit COMT (due to the Tea Polyphenols content of Green Tea).
> Saint John’s Wort may inhibit the excessive destruction of Catecholamines by COMT.
> Siberian Ginseng may inhibit COMT.
>
>
Posted by linkadge on November 4, 2006, at 10:38:51
In reply to Re: resveratrol improves lifespan, makes you manic, posted by qqqsimmons on November 4, 2006, at 9:55:34
Alzheimers drugs like aricept are acetylcholinsterase inhibitors. Acetylcholinsterase degreades acetycholine, so an acetycholnsterase inhibitor prolongs the life of acetycholine, which is supposed to affect some aspects of human memory.
Linkadge
Posted by qqqsimmons on November 4, 2006, at 12:23:57
In reply to Re: resveratrol improves lifespan, makes you manic, posted by linkadge on November 4, 2006, at 10:38:51
thanks for the info.
i wonder if consuming lots of calcium also inhibits COMT:
###
Calcium inhibition of rat liver catechol-O-methyltransferase*1Abstract
The activity of partially purified rat liver catechol-O-methyltransferase (COMT) was measured by an assay procedure in which 3,4-dihydroxybenzoic acid was used as a substrate for the enzyme. Optimal enzyme activity was present at a concentration of MgCl2 of 10−3 M. The effects on COMT activity of a series of alkaline earth compounds were determined in the presence of optimal concentrations of MgCl2. CaCl2 and Ca(NO3)2 at concentrations of 10−3 M reduced COMT activity by 63 and 59 per cent respectively. BaCl2 and Sr(NO3)2 (10−3 M) did not decrease enzyme activity, nor did additional MgCl2 to a final [Mg2+] of 2 × 10−3 M) did not decrease enzyme activity and 0·50 × 10−3 M CaCl2 in the presence of different concentrations of 3,4-dihydroxybenzoic acid, S-adenosyl-1-methionine and MgCl2 was determined. In each case Lineweaver-Burk plots of these data were compatible with noncompetitive or “mixed” inhibition.###
Catechol-o-methyltransferase in rat erythrocyte and three other tissues: comparison of biochemical properties after removal of inhibitory calcium.Quiram DR, Weinshilboum RM.
Clinical Pharmacology Unit, Departments of Pharmacology and Internal Medicine, Mayo Foundation, Rochester, MN 55901, USA.The biochemical characteristics of soluble catechol-O-methyltransferase (COMT) activity in rat erythrocytes were compared with the properties of the soluble enzyme in rat liver, heart, and brain. COMT was measured by a procedure that avoided artifacts of some other assay procedures including inhibition of the enzyme by endogenous calcium. After the removal of calcium from the reaction mixture the apparent Michaelis-Menten constants for the two cosubstrates of the COMT reaction, S-adenosyl-1-methionine (SAM) and 3,4-dihydroxybenzoic acid (DBA), were similar in tissue preparations of rat liver, brain, heart and blood. The apparent Km values for the four tissues ranged from 5.7 to 6.7 x 10(-6) M and from 0.9-1.4 x 10(-4) M for SAM and DBA, respectively. The optimal pH and the optimal concentration of magnesium for the assay of red blood cell COMT were also similar to those for the enzyme in the three other rat tissues. After the removal of endogenous calcium, COMT activity in all four tissues was inhibited by the addition of calcium, and the [CaCl2] necessary to inhibit the enzyme activity 50% was 3-5 x 10(-4) M in all cases. The relative activities of COMT in the rat heart, brain, erythrocyte, and liver when expressed per g tissue or per ml of packed red blood cells were 1 to 1.15 to 1.58 to 140, respectively.
> Alzheimers drugs like aricept are acetylcholinsterase inhibitors. Acetylcholinsterase degreades acetycholine, so an acetycholnsterase inhibitor prolongs the life of acetycholine, which is supposed to affect some aspects of human memory.
>
>
>
> Linkadge
Posted by qqqsimmons on November 4, 2006, at 16:23:42
In reply to Re: resveratrol improves lifespan, makes you manic, posted by linkadge on November 2, 2006, at 19:40:15
> Actually, I am interested in compounds that could increase monoamine oxidase activity.
>
> Linkadgethe closest i could find is flavin adenine dinucleotide (FAD), a cofactor in monoamine oxidase. can't buy FAD, that i know of, but i guess it's made from riboflavin, vitamin B2. can't find info about riboflavin boosting MOA activity, but who knows...
i guess someone will have to take excessive riboflavin and see if they start to feel depressed???
it looks like they're still trying to figure out the structure of MAO-A...
Posted by Tomatheus on November 9, 2006, at 18:15:15
In reply to Re: resveratrol improves lifespan, makes you manic, posted by linkadge on November 2, 2006, at 19:40:15
> Actually, I am interested in compounds that could increase monoamine oxidase activity.
>
> LinkadgeTheoretically, copper might increase MAO activity, considering that the MAO enzymes are made from copper. However, I'm not sure to what extent the body will continue to absorb the copper that gets ingested and continue to make more MAO-A and MAO-B just as a result of an increase in the intake of copper. Another thing to consider is that copper is believed to be a cofactor in the synthesis of norepinephrine, which could theoretically counteract the effect of increasing your MAO activity.
But as far as finding something that might increase the activity of the MAO enzymes, copper is the only thing that I can think of.
Tomatheus
Posted by mr152 on April 21, 2007, at 12:49:29
In reply to resveratrol improves lifespan, makes you manic?, posted by qqqsimmons on November 2, 2006, at 10:09:04
I was taking 80 mgs daily of resveratrol for a month before starting fluoxetine at 10 mgs daily. Within 5 days on fluoxetine I was experiencing hypomania with teeth grinding. This is when I looked up and discovered the maoi properties of resveratrol.
This is the end of the thread.
Psycho-Babble Alternative | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.