Hi everyone! I went to see my psychiatrist, and she wants me to go to the Cleveland clinic to get a brain scan done. I sm Hoping that this test can do something for me. I told my psychiatrist about everything, including not being able to feel emotions anymore, and feeling as if I had no dopamine left. She is also putting me on new medications. I will give everyone an update after all the testing and stuff.
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Mental Health Coming off Invega Sustenna (Paliperidone) v3
- Thread starter NOtoInvega
- Start date
- Status
deleted-user01120519
Bluelighter
- Joined
- Aug 8, 2018
- Messages
- 478
I hope you get banned forever from this forum by order of the Peaky Blinders XD
CanadianScott
Greenlighter
Look into neuroleptic induced deficit syndrome.
If you think that's what you're experiencing, tell your psychiatrist this.
I think neuroleptic induced deficit syndrome is what most of us here are dealing with.
I would reccomend trying to look towards getting off all medication if you can in the future too.
That is if you and your psychiatrist are 100% sure it will be safe.
They will be reluctant to do this though but alot of the times YOU know what's best for YOUR body and brain.
Update for all:
I recieved 3 injections just under 9 months ago.
I have improved alot!
I'm able to laugh, cry and feel emotions.
Maybe not as strong as before, but I can definitely feel them.
My sex drive has improved to 75% of what it used to be and I'm producing larger amounts of semen and it's not always clear (sorry for being graphic).
Still haven't regained full sensitivity on my knob though and orgasms aren't as enjoyable as before, but still nice.
Increased energy, probably around 75% of what it used to be.
Intelligence seems to have recovered somewhat.
Again, probably around 75% of what it used to be.
Just need to lose the weight I have gained, get back in shape and on track and life will be worth living again.
Cheers, I think of you all everyday and hope we can all find happiness again in life.
Invegarecovery
Bluelighter
- Joined
- Apr 26, 2018
- Messages
- 63
Invega sustenna is the perfect drug to become successful and others too like for example abilify maintena
Invegarecovery
Bluelighter
- Joined
- Apr 26, 2018
- Messages
- 63
dirtyinvega
Bluelighter
No antidepressant on the market / on planet earth can do the damage that invega has done to peoples brain/mind. Maybe it has damaged my brain less then 5%. But it wholly was invega 95%.
PhucInvega
Bluelighter
- Joined
- Feb 25, 2019
- Messages
- 98
Where do you get this information from that SJW is placebo? I'm using it solely for the purpose that it induces the P-glycoprotein which pumps foreign substances out from cells into the blood. How is that a placebo effect? You release paliperidone from your cells with the power of your mind? That's some jedi mind tricks shit over there bro, please teach me. And as for the depression, in Germany, SJW is the go-to medication when someone is having a depressive episode. It has been shown to be as effective in treatment of depression as Prozac and sertraline. If you haven't even tried it, how can you be so sure? And funny enough, both risperidone and paliperidone INHIBIT the P-gp, so less will be metabolized.
"Risperidone (RSP) and its major active metabolite, 9-hydroxy-risperidone (paliperidone, PALI), are substrates of the drug transporter P-glycoprotein (P-gp)."
Risperidone and paliperidone inhibit p-glycoprotein activity in vitro - PubMed
Risperidone (RSP) and its major active metabolite, 9-hydroxy-risperidone (paliperidone, PALI), are substrates of the drug transporter P-glycoprotein (P-gp). The goal of this study was to examine the in vitro effects of RSP and PALI on P-gp-mediated transport. The intracellular accumulation of...www.ncbi.nlm.nih.gov
"Cyclosporine and sirolimus are P-glycoprotein (Pgp) substrates "
Role of P-glycoprotein in cyclosporine cytotoxicity in the cyclosporine-sirolimus interaction - PubMed
Cyclosporine nephrotoxicity remains a major side effect in solid organ transplantation, and can be exacerbated by concomitant administration of sirolimus. Cyclosporine and sirolimus are P-glycoprotein (Pgp) substrates. We hypothesized that the Pgp activity level may affect cyclosporine...
What is St. John's wort doing to cause a reduction in the concentrations of cyclosporine? (Could as well be paliperidone or risperidone since they're all subtrates of P-gp)
How does St. John's wort influence CYP3A4 and Pgp activity which is known to reduce cyclosporine concentrations?
- In order to understand this, a basic review of the metabolic and elimination pathways for cyclosporine are needed.
- Cyclosporine's metabolism is dependent on the presence and function of the cytochrome P450 (CYP) 3A4 enzyme, which means cyclosporine is a substrate CYP3A4.(6,7)
- Furthermore, cyclosporine's elimination from cells and ultimately from the body is partially mediated by P-glycoprotein (Pgp), which makes it also a substrate for Pgp.(8,9)
- These two pathways of clearance are important to understanding why St. John's wort causes cyclosporine concentrations to decrease.
- For purposes of being complete, cyclosporine is a also a potent inhibitor of several influx cell membrane transporters (OATP1B1, OATP1B3, OATP2B1) as well as the efflux cell membrane transporters (MRP2 and P-gp).(8,10) As such, it is evident why drug-drug interactions between cyclosporine and other medications are not only complex, but cannot be easily or fully explained by the a simple comparison of the CYP450 enzyme pathways between two or more medications.
- St. John's wort is a substrate for the activation of the pregnane X receptor (PXR), which is a well known nuclear receptor found in the cytoplasm of various cells, including liver and gastrointestinal cells.(11,12)
- The PXR is important because it is one of the transcription factors known to influence gene expression of both CYP3A4 and Pgp within the nucleus of hepatic and intestinal cells.(12,13)
- Therefore, any substrate that activates PXR will also increase the gene expression of CYP3A4, which will make more CYP3A4 enzyme available to metabolize more cyclosporine and increase the expression of Pgp, which will increase the presence of Pgp mediated efflux of cyclosporine.
How does St. John's wort actually increase the gene transcription of both CYP3A4 and Pgp inside the cell?
- St. John's wort is an herb that is derived from the tops of the flowering parts of Hypericum perforatum L. and is known to have several active ingredients which include cyclopseudohypericin, hypericin, hyperforin, isohypericin, protohypericin, pseudohypericin and several other flavonoids.(14) As it relates to these ingredients, hyperforin specially is a substrate, or activator, of PXR.(11)
- As mentioned before, PXR is a nuclear receptor found in the cytoplasm of cells. It has 3 major domains that influence its function and level of activity on gene expression. The first domain, (activation function 1 (AF-1) domain) located at the amino terminus, is where recognition of other transcription factors and/or co-activators cause ligand-independent activation. The second domain (DNA-binding domain) is the part that directly binds to DNA to modulate gene transcription. The third domain (ligand-binding domain) on PXR is where substrates, like drugs, bind to "activate" the transcription of more genes.
- Therefore, as St John's wort passes through the cell membrane, by diffusion or transport, it will bind to the ligand-binding domain of PXR in the cytoplasm. This causes a dissociation of the histone deacetylase-containing complex (transcriptions co-repressors) so that PXR can then enter the nucleus. Once in the nucleus of the cell, the ligand-receptor complex either recruits co-activators to form a homodimer or heterodimer with the retinoid X receptor (RXR), where it can now bind to response elements in the promoter and enhancer regions of the target gene. Once this occurs, gene transcription for CYP3A4 is turned on as well as activation of the ABCB1gene, which is needed to make Pgp.
- The more CYP3A4 and Pgp transcribed, the greater the ability to metabolize medications known to be a substrate for CYP3A4 and eliminate substrates of Pgp from inside the cell, thereby accelerating their clearance from the body.
After further research and experiments with @earwiggs , I have came to a conclusion that it's best to wait at least 4 (1-2 shots), 5 (3-4 shots) to 6 (5+ shots) months since your last injection, before you start using SJW, because it accelerates the metabolism (due to CYP-enzyme and P-gp induction) by a great degree. Also make sure you are not on any medication if you decide to use SJW, since it also accelerates the metabolism of like 95% of the current drugs on the market.
Hypericin in SJW is the compound responsible for the enzyme/protein inductions. Comparison between different SJW products;
A message I sent to @lifeline a while ago;
"I've been using St. John's Wort for 3 days now at 875 mgs a day. Before I started taking it I had this irritating feeling every morning. I just had to get up from bed instantly and go for a smoke and it would fade out. But if I stayed in bed, the feeling would just get worse. Well, the feeling is now all gone. The SJW is definately doing something. I would recommend giving it a shot. SJW inhibits the reuptake of serotonin, dopamine, noradrenaline and l-glutamate. It also binds to GABA-A and -B sites and that way acts like a very mild benzo. It also inhibits monoamine oxidase A and B which break down serotonin and dopamine etc. And on top of that it induces enzymes in the liver which metabolize and break down pharmaceuticals. And on top of that it induces the P-glycoprotein which pumps out the foreign substances from the cells through the cell's membrane."
I have done further research aswell (1K_Seteli), but the research doesn't deal with pharmacology though;
And to the room;
it is possible to recover 100%. I would say I'm 110% the person I was before the shots. Use your situation for good. I have no fears after this literal poisoning. Everything feels so fucking awesome, when it was all taken away for a while. You start to appreciate things, after you realize you lost them. The mindset is what matters.
Anyone that has gone through this horrible experience, has gone through hell. Not biblical hell, since that doesn't exist, but the REAL HELL. But there is a way out, and I know the way. And so do you now.
Feel free to send me a private message if you have any questions, I'll be happy to answer them,
Shanti!
E: I give all of you my word. Anyone who has had to go through this horrible experience, you shall be rewarded for not giving up. That's a promise. PM me, tell me about your situation, how many shots did you get, what was the reason, etc. I will one day go through all of them, one by one. I will listen and help all of you. Love is what we all need. Love is all there is in the end.
The doctors that have made a vow, have broke their vow, by poisoning ill, and innocent patients. When I was forcibly hospitalized, I showed my research on cannabinoids, flavonoids, terpenes and other medicinal compounds in the plants to the head shrink. I also showed him straight facts how his medication is literal poisoning, and how e.g. CBD can treat psychotic illnesses at high doses. Depression/PTSD/anxiety etc. can all be cured, not just disguised, with compounds found in the nature. I started my study, or whatever, by quoting the Hippocratic Oath, which is the doctors vow. I gave the doctor an alternative for his toxins, yet he still poisoned me for no reason. The rats even seized my laptop and phone for three weeks, and once I got them back I noticed that someone had tried to login to my laptop, since the PIN code was locked due to too many incorrect logins. Fucking rats. If my research wasn't valid, why the fuck would you try to login to a "psychotic" persons laptop? No rational reason. You just saw me as a threat. You were right. I was. And still am. Funny thing is, I wasn't even in psychosis. Like I told you Jaakko, I was there on purpose. But you didn't believe me. How about now? Fool.
"I swear by Apollo Physician, by Asclepius, by Hygieia, by Panacea, and by all the gods and goddesses, making them my witnesses, that I will carry out, according to my ability and judgment, this oath and this indenture.
To hold my teacher in this art equal to my own parents; to make him partner in my livelihood; when he is in need of money to share mine with him; to consider his family as my own brothers, and to teach them this art, if they want to learn it, without fee or indenture; to impart precept, oral instruction, and all other instruction to my own sons, the sons of my teacher, and to indentured pupils who have taken the physician’s oath, but to nobody else.
I will use treatment to help the sick according to my ability and judgment, but never with a view to injury and wrong-doing. Neither will I administer a poison to anybody when asked to do so, nor will I suggest such a course. Similarly I will not give to a woman a pessary to cause abortion. But I will keep pure and holy both my life and my art. I will not use the knife, not even, verily, on sufferers from stone, but I will give place to such as are craftsmen therein.
Into whatsoever houses I enter, I will enter to help the sick, and I will abstain from all intentional wrong-doing and harm, especially from abusing the bodies of man or woman, bond or free. And whatsoever I shall see or hear in the course of my profession, as well as outside my profession in my intercourse with men, if it be what should not be published abroad, I will never divulge, holding such things to be holy secrets.
Now if I carry out this oath, and break it not, may I gain for ever reputation among all men for my life and for my art; but if I break it and forswear myself, may the opposite befall me."
See you soon, mr "doctor", Jaakko Paavilainen.
You tried to fuck with the Queen, but the Queen will fuck YOU instead, fucking scumbag lowlife gender disequal 'cannot comprehend my own existence' motherfucker. Rat. Fool. Maybe it's the doctors turn to taste his own "medicine" now. What do you guys think?
'Til we meet. Running is pointless. Hiding is pointless. I am everywhere. I will come up on infrared. I can see you when you're asleep in the darkness. I am the Lord of the Darkness. The Lord of the Anti-light. The anti-christ. 666
Vitun rotta. Sä tiiät ketä mä oon. Mä tiiän sen. Mut onks sul todisteita?
No onhan sulla, silmä käteen ja kato. Mut mitäs meinasit tehdä? Tappaa mut? Soittaa poliisit?
Onks tä ees totta? Mitä helvettiä Jaakko? Ei näin voi käydä. Näin käy vaan saduissa. Entä jos ootkin unessa? Nipistä itteäs.
Mul on sulle vinkki; ota vähän paliperidonia, se auttaa. Oot selvästikin psykoosissa.
Joku veti sieniä ja hasista sun vitun sairaalassas mouho.
Sun vitun alainen salakuljetti jollekkin 2 grammaa hasista, ilman et se alainen ees tiesi siitä. Luuliks et on olemas kahleita jotka mua pidättelis?
Tiiätkö mitä sul käy kun kuolet? Mä tiiän. Se ei oo sun kohalla ainakaan mitään kauheen kivaa
Tutiseeks vähän kädet, ja alahuuli väpättää? Mä tiiän senkin. Mä tiiän kaiken. Kaiken mitä säkin oot tehny. Ja tuut tekee. IHAN KAIKEN.
Mieti sitä.
ॐ नमः शिवाय
Devīsūkta - Wikipedia
Attachments
Last edited:
ChemicalLobotomy
Greenlighter
- Joined
- Nov 21, 2019
- Messages
- 1
YES PLEASE!!!! DO IT!!!! THIS SHIT HAS KILLED ME FROM THE INSIDE!!!!
Invegarecovery
Bluelighter
- Joined
- Apr 26, 2018
- Messages
- 63
For me it hasnt
After further research and experiments with @earwiggs , I have came to a conclusion that it's best to wait at least 4 (1-2 shots), 5 (3-4 shots) to 6 (5+ shots) months since your last injection, before you start using SJW, because it accelerates the metabolism (due to CYP-enzyme and P-gp induction) by a great degree. Also make sure you are not on any medication if you decide to use SJW, since it also accelerates the metabolism of like 95% of the current drugs on the market.
Hypericin in SJW is the compound responsible for the enzyme/protein inductions. Comparison between different SJW products;
A message I sent to @lifeline a while ago;
"I've been using St. John's Wort for 3 days now at 875 mgs a day. Before I started taking it I had this irritating feeling every morning. I just had to get up from bed instantly and go for a smoke and it would fade out. But if I stayed in bed, the feeling would just get worse. Well, the feeling is now all gone. The SJW is definately doing something. I would recommend giving it a shot. SJW inhibits the reuptake of serotonin, dopamine, noradrenaline and l-glutamate. It also binds to GABA-A and -B sites and that way acts like a very mild benzo. It also inhibits monoamine oxidase A and B which break down serotonin and dopamine etc. And on top of that it induces enzymes in the liver which metabolize and break down pharmaceuticals. And on top of that it induces the P-glycoprotein which pumps out the foreign substances from the cells through the cell's membrane."
I have done further research aswell (1K_Seteli), but the research doesn't deal with pharmacology though;
And to the room;
it is possible to recover 100%. I would say I'm 110% the person I was before the shots. Use your situation for good. I have no fears after this literal poisoning. Everything feels so fucking awesome, when it was all taken away for a while. You start to appreciate things, after you realize you lost them. The mindset is what matters.
Anyone that has gone through this horrible experience, has gone through hell. Not biblical hell, since that doesn't exist, but the REAL HELL. But there is a way out, and I know the way. And so do you now.
Feel free to send me a private message if you have any questions, I'll be happy to answer them,
Shanti!
E: I give all of you my word. Anyone who has had to go through this horrible experience, you shall be rewarded for not giving up. That's a promise. PM me, tell me about your situation, how many shots did you get, what was the reason, etc. I will one day go through all of them, one by one. I will listen and help all of you. Love is what we all need. Love is all there is in the end.
The doctors that have made a vow, have broke their vow, by poisoning ill, and innocent patients. When I was forcibly hospitalized, I showed my research on cannabinoids, flavonoids, terpenes and other medicinal compounds in the plants to the head shrink. I also showed him straight facts how his medication is literal poisoning, and how e.g. CBD can treat psychotic illnesses at high doses. Depression/PTSD/anxiety etc. can all be cured, not just disguised, with compounds found in the nature. I started my study, or whatever, by quoting the Hippocratic Oath, which is the doctors vow. I gave the doctor an alternative for his toxins, yet he still poisoned me for no reason. The rats even seized my laptop and phone for three weeks, and once I got them back I noticed that someone had tried to login to my laptop, since the PIN code was locked due to too many incorrect logins. Fucking rats. If my research wasn't valid, why the fuck would you try to login to a "psychotic" persons laptop? No rational reason. You just saw me as a threat. You were right. I was. And still am. Funny thing is, I wasn't even in psychosis. Like I told you Jaakko, I was there on purpose. But you didn't believe me. How about now? Fool.
"I swear by Apollo Physician, by Asclepius, by Hygieia, by Panacea, and by all the gods and goddesses, making them my witnesses, that I will carry out, according to my ability and judgment, this oath and this indenture.
To hold my teacher in this art equal to my own parents; to make him partner in my livelihood; when he is in need of money to share mine with him; to consider his family as my own brothers, and to teach them this art, if they want to learn it, without fee or indenture; to impart precept, oral instruction, and all other instruction to my own sons, the sons of my teacher, and to indentured pupils who have taken the physician’s oath, but to nobody else.
I will use treatment to help the sick according to my ability and judgment, but never with a view to injury and wrong-doing. Neither will I administer a poison to anybody when asked to do so, nor will I suggest such a course. Similarly I will not give to a woman a pessary to cause abortion. But I will keep pure and holy both my life and my art. I will not use the knife, not even, verily, on sufferers from stone, but I will give place to such as are craftsmen therein.
Into whatsoever houses I enter, I will enter to help the sick, and I will abstain from all intentional wrong-doing and harm, especially from abusing the bodies of man or woman, bond or free. And whatsoever I shall see or hear in the course of my profession, as well as outside my profession in my intercourse with men, if it be what should not be published abroad, I will never divulge, holding such things to be holy secrets.
Now if I carry out this oath, and break it not, may I gain for ever reputation among all men for my life and for my art; but if I break it and forswear myself, may the opposite befall me."
See you soon, mr "doctor", Jaakko Paavilainen.
You tried to fuck with the Queen, but the Queen will fuck YOU instead, fucking scumbag lowlife gender disequal 'cannot comprehend my own existence' motherfucker. Rat. Fool. Maybe it's the doctors turn to taste his own "medicine" now. What do you guys think?
'Til we meet. Running is pointless. Hiding is pointless. I am everywhere. I will come up on infrared. I can see you when you're asleep in the darkness. I am the Lord of the Darkness. The Lord of the Anti-light. The anti-christ. 666
Vitun rotta. Sä tiiät ketä mä oon. Mä tiiän sen. Mut onks sul todisteita?
No onhan sulla, silmä käteen ja kato. Mut mitäs meinasit tehdä? Tappaa mut? Soittaa poliisit?
Onks tä ees totta? Mitä helvettiä Jaakko? Ei näin voi käydä. Näin käy vaan saduissa. Entä jos ootkin unessa? Nipistä itteäs.
Mul on sulle vinkki; ota vähän paliperidonia, se auttaa. Oot selvästikin psykoosissa.
Joku veti sieniä ja hasista sun vitun sairaalassas mouho.
Sun vitun alainen salakuljetti jollekkin 2 grammaa hasista, ilman et se alainen ees tiesi siitä. Luuliks et on olemas kahleita jotka mua pidättelis?
Tiiätkö mitä sul käy kun kuolet? Mä tiiän. Se ei oo sun kohalla ainakaan mitään kauheen kivaa
Tutiseeks vähän kädet, ja alahuuli väpättää? Mä tiiän senkin. Mä tiiän kaiken. Kaiken mitä säkin oot tehny. Ja tuut tekee. IHAN KAIKEN.
Mieti sitä.
ॐ नमः शिवाय
ommm namah sadashivayah
Devīsūkta - Wikipedia
en.wikipedia.org
View attachment 17516
Blabla lol
Seriously 11 years of antiosychotic and Antidepressant that very strange bro
Bro you need one years for he get out of you systèm its just not possible what you Say im too négative i know but all people i meet they never recovered from invega we need live life without émotion feeling motivation energy that its true its life i wish antipsychotiques33 dont commit suicide m'y question some people commit suicide because its too much some no so i dont understand because live like this its really too hard wake up without feeling
Wouahhh live without émotion its really nice bro
I remember you Say you still live you life but seriously live like that is really horrible i dont know how you Can work without feeling its really strange you like life lol
Why you like that bro because i told you you dont recover that its true bro you dont and never recover only 21 they destroy you life bro im sorry for you
No because vibration from invega like boom boom everywhere in thé body and in brain like ring Bell you have Again or no?
You really think in 11 years if st John wort is thé antidote people know but he Do nothing i think you obseded by st John wort because you Hope but its a bullshit i take st John wort thé best in thé market for 5 month everyday nothing !!!! Bullshit so stop be a scientist do you life found girlfriend go in night club do you life if you recovered broWhere do you get this information from that SJW is placebo? I'm using it solely for the purpose that it induces the P-glycoprotein which pumps foreign substances out from cells into the blood. How is that a placebo effect? You release paliperidone from your cells with the power of your mind? That's some jedi mind tricks shit over there bro, please teach me. And as for the depression, in Germany, SJW is the go-to medication when someone is having a depressive episode. It has been shown to be as effective in treatment of depression as Prozac and sertraline. If you haven't even tried it, how can you be so sure? And funny enough, both risperidone and paliperidone INHIBIT the P-gp, so less will be metabolized.
"Risperidone (RSP) and its major active metabolite, 9-hydroxy-risperidone (paliperidone, PALI), are substrates of the drug transporter P-glycoprotein (P-gp)."
Risperidone and paliperidone inhibit p-glycoprotein activity in vitro - PubMed
Risperidone (RSP) and its major active metabolite, 9-hydroxy-risperidone (paliperidone, PALI), are substrates of the drug transporter P-glycoprotein (P-gp). The goal of this study was to examine the in vitro effects of RSP and PALI on P-gp-mediated transport. The intracellular accumulation of...
"Cyclosporine and sirolimus are P-glycoprotein (Pgp) substrates "
Role of P-glycoprotein in cyclosporine cytotoxicity in the cyclosporine-sirolimus interaction - PubMed
Cyclosporine nephrotoxicity remains a major side effect in solid organ transplantation, and can be exacerbated by concomitant administration of sirolimus. Cyclosporine and sirolimus are P-glycoprotein (Pgp) substrates. We hypothesized that the Pgp activity level may affect cyclosporine...
What is St. John's wort doing to cause a reduction in the concentrations of cyclosporine? (Could as well be paliperidone or risperidone since they're all subtrates of P-gp)
How does St. John's wort influence CYP3A4 and Pgp activity which is known to reduce cyclosporine concentrations?
- In order to understand this, a basic review of the metabolic and elimination pathways for cyclosporine are needed.
- Cyclosporine's metabolism is dependent on the presence and function of the cytochrome P450 (CYP) 3A4 enzyme, which means cyclosporine is a substrate CYP3A4.(6,7)
- Furthermore, cyclosporine's elimination from cells and ultimately from the body is partially mediated by P-glycoprotein (Pgp), which makes it also a substrate for Pgp.(8,9)
- These two pathways of clearance are important to understanding why St. John's wort causes cyclosporine concentrations to decrease.
- For purposes of being complete, cyclosporine is a also a potent inhibitor of several influx cell membrane transporters (OATP1B1, OATP1B3, OATP2B1) as well as the efflux cell membrane transporters (MRP2 and P-gp).(8,10) As such, it is evident why drug-drug interactions between cyclosporine and other medications are not only complex, but cannot be easily or fully explained by the a simple comparison of the CYP450 enzyme pathways between two or more medications.
- St. John's wort is a substrate for the activation of the pregnane X receptor (PXR), which is a well known nuclear receptor found in the cytoplasm of various cells, including liver and gastrointestinal cells.(11,12)
- The PXR is important because it is one of the transcription factors known to influence gene expression of both CYP3A4 and Pgp within the nucleus of hepatic and intestinal cells.(12,13)
- Therefore, any substrate that activates PXR will also increase the gene expression of CYP3A4, which will make more CYP3A4 enzyme available to metabolize more cyclosporine and increase the expression of Pgp, which will increase the presence of Pgp mediated efflux of cyclosporine.
How does St. John's wort actually increase the gene transcription of both CYP3A4 and Pgp inside the cell?
- St. John's wort is an herb that is derived from the tops of the flowering parts of Hypericum perforatum L. and is known to have several active ingredients which include cyclopseudohypericin, hypericin, hyperforin, isohypericin, protohypericin, pseudohypericin and several other flavonoids.(14) As it relates to these ingredients, hyperforin specially is a substrate, or activator, of PXR.(11)
- As mentioned before, PXR is a nuclear receptor found in the cytoplasm of cells. It has 3 major domains that influence its function and level of activity on gene expression. The first domain, (activation function 1 (AF-1) domain) located at the amino terminus, is where recognition of other transcription factors and/or co-activators cause ligand-independent activation. The second domain (DNA-binding domain) is the part that directly binds to DNA to modulate gene transcription. The third domain (ligand-binding domain) on PXR is where substrates, like drugs, bind to "activate" the transcription of more genes.
- Therefore, as St John's wort passes through the cell membrane, by diffusion or transport, it will bind to the ligand-binding domain of PXR in the cytoplasm. This causes a dissociation of the histone deacetylase-containing complex (transcriptions co-repressors) so that PXR can then enter the nucleus. Once in the nucleus of the cell, the ligand-receptor complex either recruits co-activators to form a homodimer or heterodimer with the retinoid X receptor (RXR), where it can now bind to response elements in the promoter and enhancer regions of the target gene. Once this occurs, gene transcription for CYP3A4 is turned on as well as activation of the ABCB1gene, which is needed to make Pgp.
- The more CYP3A4 and Pgp transcribed, the greater the ability to metabolize medications known to be a substrate for CYP3A4 and eliminate substrates of Pgp from inside the cell, thereby accelerating their clearance from the body.
Only side effect is anxiety no you dont have émotions only anxiety that its true dont stop you injection bro you have Big problème in you mind bro believe me because you give false Hope since one years and people commit suicide because you speak a Big bullshit
- Status