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Ursprungligen postat av
Ennago
Går just nu på Brintellix (Vortioxetin), som är en typ av SSRI (SRI). Denna ska inte ska kombineras med icke-selektiva monoaminoxidashämmare eller selektiva MAO-A-hämmare.
Pterostilbene hämmar ju MAO-B, det vill säga är en icke-selektiv monoaminoxidashämmare och bör då inte kombineras med mitt läkemedel?
https://sv.wikipedia.org/wiki/Monoam...ash%C3%A4mmare
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364133/
Selectivity of Dietary Phenolics for Inhibition of Human Monoamine Oxidases A and B
"Resveratrol is a potent competitive inhibitor of MAO-A in rat brain with IC50 of 2 μM and Ki of 2.5 μM [12]. Resveratrol was also previously reported to be an inhibitor of MAO-A but did not significantly inhibit MAO-B up to 10μM [18], which is consistent with our study in which resveratrol showed a relatively high IC50 value for MAO-B of 15.8μM (Table 1). Pterostilbene has never been reported as an MAO inhibitor, but it was the most potent MAO-B inhibitor in our study, with an IC50 of 0.138 μM."
"
The most potent inhibitor for MAO-A was resveratrol followed by isoeugenol, curcumin, pterostilbene, zingerone, and guaiacol in descending order of potency.
The most potent inhibitor for MAO-B was pterostilbene followed by curcumin, resveratrol, isoeugenol, and guaiacol in descending order of potency.."
"..
Additionally, the selectivity indices expressed as the ratios of MAO-B/MAO-A IC50 values (Table 1) showed that resveratrol and isoeugenol are selective MAO-A inhibitors,
while pterostilbene is a selective MAO-B inhibitor. These data are especially intriguing, considering that only two methyl groups differentiate resveratrol and pterostilbene.
Besides resveratrol, isoeugenol showed the next highest level of potency and selectivity for MAO-A. Isoeugenol has a methylated catechol moiety (as do zingerone and guaiacol) and also a hydrophobic side chain, which may contribute to its MAO-A inhibition exceeding those of zingerone and guaiacol. Furthermore, among the glucosides of resveratrol and pterostilbene tested herein, MAO-A was inhibited only by resveratrol 4'-glucoside, while MAO-B was not inhibited. This is consistent with the loss of inhibitory activity by glycosides of kaempferol.."
"
Phenolic compounds are substrates for neither MAO-A or MAO-B and, unlike other MAO, substrates and inhibitors are devoid of any nitrogen atoms. The mechanism of the inhibition of phenolic compounds on MAO is not clear, but none of them was reported to have irreversible inhibition on MAO-A or MAO-B [8, 9].
The researchers found that they are reversible inhibitors with various mode of inhibition such as competitive inhibition, non-competitive, or mixed-type inhibition [8, 9]. Furthermore, several flavonoids have been established as reversible and competitive inhibitors [15].
The drug-drug interaction index (unbound Cmax/Ki [53]) for MAO-A is in the range of 2.7 × 10−3 to 0.97. Thus at high resveratrol doses (5.0 g), inhibition of MAO-A may occur. However, the drug-drug interaction index for MAO-B is in the range of 5.7 × 10−5 to 0.021, making clinically relevant MAO-B interactions with resveratrol unlikely. As with many other natural phenolic compounds, human plasma concentration data and absolute oral bioavailability for oral doses of pterostilbene are lacking [54], making predictions of gastrointestinal or systemic MAO-B interactions speculative.
A human clinical study with pterostilbene shows that 125mg twice daily orally for 6-8 weeks reduces both systolic and diastolic blood pressure, although it slightly raised plasma low-density lipoproteins [55]. Another clinical study with pterostilbene 50mg in combination with nicotinamide riboside 250mg for two months also reduced diastolic blood pressure [56].
Acute, severe, systemic MAO inhibition is expected to increase blood pressure and result in serotonin syndrome [2]; however, such adverse reactions were not reported in these studies. As with many dietary compounds, the absolute oral bioavailability of pterostilbene has not been reported, but animal studies show that it is much greater than that of resveratrol [43]. Additional studies are required to determine the absolute oral bioavailability of pterostilbene and other potentially beneficial phenolic compounds and to establish their antiaging effects on human cardiac and neuronal tissues.
"In conclusion, we applied a previously validated kynuramine-based MAO activity assay with HPLC separation and fluorescence detection for determining the inhibition and selectivity of several phenolic compounds. Among the compounds tested, resveratrol was potent and selective for MAO-A inhibition, while pterostilbene was potent and selective for MAO-B inhibition. Both compounds appeared to be competitive, time-independent inhibitors. Our calculations suggest that high doses of resveratrol have the potential to inhibit MAO-A in the gastrointestinal tract. Human pharmacokinetic studies with oral dosing of pterostilbene will facilitate future predictions of its clinical potential to interact with MAO-B in the gastrointestinal tract, liver, or systemic circulation. The anti-aging potential of these compounds is worth further investigations."
Citat:
Ursprungligen postat av
Ennago
Inser att min senaste frågeställning var luddig.
Det jag ville ha klarhet är om Pterostilbene räknas som en "icke-selektiv monoaminoxidashämmare" och därmed inte borde kombineras med mitt läkemedel eller andra SSRI (escitalopram etc har samma skrivning)?
Jag tolkar det som att icke-selektiva monoaminoxidashämmare menas med MAOI som både hämmar MAO-A och MAO-B? Jag tolkar det på detta som att det är just MAO-A man ska undvika att hämma med något annat medan selektiv MAO-B eventuellt skulle kunna fungera ändå? Däremot säger ju studierna inkl. ovan att "pterostilbene may increase the effect of sertraline". Oklart vad det innebär för mig. Om det är så som med Agmatine, att det gör effekten bättre utan risker, eller att det är risk för serotonergt syndrom?
Som du ser i det citerade svaret ovan, så klippte jag ut lite från studien ovan.
Både Resveratrol & Pterostilbene är
reversibla MAO-hämmare.
Resveratrol är dock mest selektiv för MAO-A hämning och Pterostilbene är mest selektiv för MAO-B hämning. [b]Dock skär de in lite i varandra och kan inhibera både MAO-A & MAO-B enzymerna[/B].
Pterostilbene, som jag förstår det har alltså negligerbart affinitet mot MAO-A och är allra mest selektiv för MAO-B.
Du får tänka på att de hämmar även olika enzymer, och kan alltså inverka på metabolismen av läkemedel.
Jag tar som sagt inte Pterostilbene varje dag, utan tar en låg dos Mianserin, 7.5mg mot insomnia varje kväll och tar Pterostilbene vid behov som potent nootropika, ungefär varannan dag eller vart tredje dag. Jag märker inte av några interaktioner förutom att Pterostilbenet är så starkt att jag har svårt att somna.
Jag tar en dos på runt 50mg Pterostilbene.
Jag tror att om Pterostilbene ökar effektiviteten av SSRIn Sertraline, så kan du prova en låg dos Pterostilbene, typ 25mg och se hur du reagerar på det om du tar Vortioxetine ett par dagar.
Doseringen av läkemedlet du tar och Pterostilbene är nyckeln här.
Låga doser av Vortioxetine innebär minskad total risk.
Agmatine är inte en MAO-hämmare, och är irrelevant i dessa diskussioner - som jag sa i andra trådar kan Agmatine kombineras med i princip all psykofarmaka.
Blanda inte ihop Pterostilbene och Agmatine - helt skilda substanser.