How is BREXPIPRAZOLE different from ARIPIPRAZOLE? | Mechanism of action of REXULTI | Dr Rege
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- Опубліковано 26 сер 2020
- Brexpiprazole [7-{4-[4-(1-benzothiophen-4-yl) piperazin-1-yl]butoxy}quinolin-2(1H)-one] is a novel atypical antipsychotic that is structurally similar to the atypical antipsychotic, aripiprazole.
#brexpiprazole #rexulti #antipsychotics
The video is about Brexpiprazole Mechanism of Action but it also covers:
-Mechanism of action of brexpiprazole compared with aripiprazole
-Brexpiprazole Side effects compared to Aripiprazole side effects
Brexpiprazole is a :
•Partial agonist of dopamine D2 receptors that is at a lower level of intrinsic activity than aripiprazole.
•Partial agonist at serotonin 5-HT1A that is at a stronger level of activity than aripiprazole.
•Potent antagonist of serotonin 5-HT2A receptors.
•Potent antagonist of noradrenaline alpha1B/2C receptors.
•Moderate affinity for histamine H1 receptors
Brexpiprazole has a lower incidence of akathisia than aripiprazole.
It has a long half-life of 86-91 hours.
It has minimal impact on prolactin levels.
It is metabolised by CYP2D6 and CYP3A4 enzymes.
To read about Antipsychotic medications and their mechanisms of action - a simplified guide 👉 psychscenehub.com/psychinsigh...
Thank you. You were very clear and answered all my questions
I wish we had such a great doctor here
Very informative. This treatment has made immensely improved my therapy for depression. With the pandemic I began to become confused and bipolar. I am safe but this regulator is amazing. Great sleep refreshed in the morning. This is new and I like it. Ty for the information. I understand every word as I am a former medical professional.
Thank you for your feedback and sharing your personal experience 🙏
I love ur videos doc!! Thank u so much!!
Glad you like them!🙏🏼
Perfect 👌
Very helpful and informative
Thanks for the feedback
Wow- THANK YOU! As a person who has been prescribed a wide range of meds for bipolar- I settled on lamictal which caused horrible hair loss- my dr suggested Rexulti - and I was hesitant because abilify caused 15 lb weight gain in a month- your video has given me a positive attitude toward this- I’m only on day three but I am more relaxed after your explanations. This information is invaluable!
Tracy M we hope it all goes well for you. 👍
PsychScene Hub much appreciated 😘I started ww today to hopefully ward off those extra lbs- 🤞🏼🤞🏼🤞🏼
More details on weight gain and it’s management in psychiatry psychscenehub.com/psychinsights/understanding-and-managing-obesity-in-mental-health-pharmacological-approaches-2/
@@TracvM320 How are you doing?
@@mauriciojr.4428 not well 😢 i’m sad to say that after six weeks the dizziness with the pills side effects as well as bloating and a 7 pound weight gain made them intolerable for me so I had to quit them. If not for extreme dizziness, and that is not an exaggeration almost to the point of passing out and it happened at least four times as well as feeling as if I could see stars in front of my eyes and my blood pressure was all over the place and I’ve never had a problem with my blood pressure. They do work very well for depressionBut the side effects for me personally we’re not worth it. Thank you though for checking on me and if you have any other questions feel free to ask :-)
Excellent explanation of dopamine modulation. I’d like to hear more opinion from you on the “me too” drugs.for example is brexpiprazole any better than Abilify? Is it sort of an optical isomer of Abilify? Less side effects? What I’m finding is most of my patients are on managed healthcare plans and the lower tiered generic meds are much much cheaper than going into the higher tiered, newer drugs, which many people can’t afford. Maybe do a comparative class on old v new.
Great questions. Brexpiprazole has some positives when used in the right target group. 25% lower partial agonist activity than aripiprazole ( so higher D2 antagonism ) - this also means lower akathisia or activating effects. But parkinsonian effects to me monitored. 10 times greater 5HT2A antagonism & 5HT1A PA lending better mood modulation properties. Alpha 1 antagonism can help with trauma ( evidence for this) . So in summary it’s been developed as a ‘better’ version of Aripip but as with all meds it’s about dose modulation and right target group. Hope that helps. Covered it in more detail here psychscenehub.com/psychinsights/brexpiprazole-psychopharmacology/
I'm also hearing great things about Cariprazine; its now approved by the FDA in the USA as an add on to antidepressants for depression. It has actions on the D3 receptors that could help a number of conditions, from what i've read. Looking forward to your review on Vraylar/Cariprazine and how it might be unique. Happy 2023!!
Good point. The D3 PA does offer a unique profile. The main side effect of akathisia is one to monitor closely. Happy Ny 🎉. Written a detailed article on cariprazine 👉psychscenehub.com/psychinsights/cariprazine-mechanism-of-action-psychopharmacology-clinical-application/
Thx again! Can patients with a high degree of anxiety and jitteriness do well on Abilify and Vraylar? appreciate the article!
@@MrDcrules depends on the Sx formulation. Anxiety, hyperarousal or agitation. Mood disorder or psychotic disorder . Medications co prescribed etc. so many variables to take into account. In summary partial agonists Ari, cari, and brexpiprazole have different profiles which when used appropriately for the right symptoms can be useful. For example if patient has high hyperarousal levels with insomnia and agitation in context of mood disorders brexpiprazole would be a ‘better’ choice due to mild anti histaminergic effect and alpha2 properties targeting these Sx. The D2 PA and 5 HT 1 A and 2 A can help with mood .
Thank you. Wishing you well in 2023. Best. Don
Learning here
I certainly hope you can shed light on this:
Trialed 1 month lowest 10mg dose Aripiprazole.
Upon withdrawal, dystonia for several weeks occurred.
What causes that? and given my reaction, does it mean atypical antipsychotics are very risky for me developing EPS in the short or long term? Is this type of reaction to withdrawal a sign I am at greater risk of developing Parkinson's disease?
I would like to try Brexpiprazole and besides the dystonia from withdrawal of Aripiprazole, would it be any less likely to cause what seemed like mixed hypomania on Aripiprazole? I thought all types of APs were safe for bipolar spectrum so was surprised Aripiprazole had that effect. I was not taking any other medicines at the time.
Thank you Dr Rege
Question: What is your marvelous head doing in front of the blackboard? Could you not move it further to the right?
Will keep that in mind 😁
I certainly hope you can shed light on this:
Trialed 1 month lowest 10mg dose Aripiprazole.
Upon withdrawal, dystonia for several weeks occurred. Abrupt withdrawal. Quetiapine taken for much longer and tapered, no dystonia upon withdrawal. No EPS on Seroquel however too sedating, not tolerated. Lurasidone at low doses did nothing for depression or side effects.
What causes that? and given my reaction, does it mean atypical antipsychotics are very risky for me developing EPS in the short or long term? Is this type of reaction to withdrawal a sign I am at greater risk of developing Parkinson's disease or Alzheimer's (acetylcholine deficiency?)? If it helps to know, when I am on SSRIs they cause tightness jaw which Buspirone reverses too.
I would like to try Brexpiprazole and besides the dystonia from withdrawal of Aripiprazole, would it be any less likely to cause what seemed like mixed hypomania on Aripiprazole? I thought all types of APs were safe for bipolar spectrum so was surprised Aripiprazole had that effect. I was not taking any other medicines at the time.
Thank you Dr Rege
It's difficult to provide any advice here on YT or to apply any comments here individually so please take that into account. Aripiprazole has very strong affinity to D2 receptors with strong intrinsic partial agonist activity. It acts as D2 agonist (activates) when DA is low; antagonist when DA is high in synaptic cleft to keep it simple. Withdrawal dystonia can occur as SE of antipsychotic withdrawal - more likely if the action was a partial agonist > antagonist which aripiprazole can have (which is also why mixed hypomania with Ari - Ari is known in some to have an activating effect) . It explains why quetiapine doesn't because quetiapine has low affinity to D2 receptors. It does not mean that one is at risk of the conditions - but your doctor is in the best position to answer this as age, medical factors, family history etc all play a part. Brexpiprazole has 25% lower intrinsic activity as a partial agonist - and is a stronger D2 antagonist > ari . Hope this helps in understanding the differences.
What if patient was on risperdal 2 mg daily, and I want to switch to Brexpiprazole ? How can I do the cross tapering between those 2 medications?
This is best done under supervision. It is a cross titration with brexpiprazole low dose started while risperidone reduction beginning at around 1 week -10 days. Approx 10 days for Brexpiprazole to reach steady state levels
Then following similar principles cross titration should occur until optimum dose is reached of brexpiprazole. Important aspect is that risperidone should not be stopped suddenly and the last dose of risperidone 0.5 or 1 mg should be stopped carefully. As you can see this requires supervision. It's not challenging as such but a balance between preventing relapse vs side effects is needed. Ps not medical advice.
How exactly does the antihistaminic action of certain anti-psychotics like Quetiapine/ Olanzapine and Mirtazepine cause sedation? how does it interact with other activating receptors/neurotransmitters?
Histamine is a neurotransmitter that plays a part in wakefulness. For example in sleep phases this histaminergic activity is reduced in specific phases for sleep to occur.
Great informational video, thank you. You're an excellent speaker. My question is if vortioxetine taken in conjunction with Rexulti would be safe, given that they both go thru gene CYP2D6?
Thank you for your feedback 🙏🏼. Neither one is an inhibitor or inducer but a substrate - so they will not increase or decrease levels - they will just be metabolised by liver in the same way. Hence both can be combined without adverse interaction. Individuals with slow CYP2D6 activity can show increased levels which can be associated with side effects. Ps not medical advice - please discuss it with your doctor.
I wonder if Rexulti can be helpful with ocd? It’s not sedating, right? Thanks for your videos! Would enjoy working with someone of your caliber in the Washington DC, USA area. Can you recommend any? Best!
Aripiprazole a partial agonist is considered as an evidence based augmentation strategy in OCD . Brexpiprazole would also be applicable based on a similar pharmacological profile. However it depends on the symptoms being targeted and intensity asking with the side effect profile that ultimately leads to the choice.
It's like voltage gated ion channels, the regulating effect is bliss...
Is aripiprazole and brexpiprazole effective for treating acute psychosis in the ED compared with other antipsychotics? In my hospital aripiprazole is seen as less effective and more as an augmentation strategy
It is best used as an augmentation strategy in acute psychosis as aripiprazole can lead to akathisia in initial stages / brexpiprazole has a lower incidence.
2. They are partial agonists and their steady state levels occur around 10-14 days.
3. Brexpiprazole has greater D2 antagonist effect as so can work well with augmentation with a more antiagitation / ‘ sedating ‘ AP with anti -H1 effect.
The advantage of this is that once the acute phase has resolved a switch can occur to brexpiprazole or aripiprazole with a better tolerability profile in terms of metabolic dysfunction, prolactin etc.
Also the sooner the switch is done, easier rhe process in terms of rebounds. Nonetheless augmentation strategies are now shown to be effective when done well.
Would topical ketoconazole raise levels of the brexpiprazole ? Or would that be more oral route? I’ve just started on brexpiprazole and use keto shampoo for hair loss
Also what is the likelihood of brexpiprazole and TD at mdd doses? A lot of videos I have watched seem to demonize atypical anytipsychotics this is the first video giving some relief.
Good question- Ketoconazole in shampoos is at 2% which is equivalent say in gel to 20 mg. You should confirm this with the pharmacist . Compared to oral ketoconazole which is 100,200,400 Ng. So unlikely to lead to significant interactions but this is something you should discuss with the pharmacist or doctor
@@tylervozza2107 it is a partial agonist - so it’s dopamine antagonism is not as strong at MDD doses. It has a lower incidence of TD compared to other stronger DA antagonists . Having said that - dose individualisation is important - at high doses for the individual EPSEs can occur .
@@PsychiatrySimplified thanks for the response!
I have a question about Rextuli and Abilify. Do they both affect H1 Receptors ? Also I have a bad experience with Serqouel and Zyprexa they made my anxiety way worse. Seems I have a problem with antihistamines has the opposite affect. I was on Abilify and was ok for a while but developed akathisa combined with Pristiq 25mg.
My question is will rextuli make my anxiety worse due to its antihistamine properties ?
Rexulti ( brexpiprazole ) had antihistaminergic action ( mild) - Abilify does not. Quetiapine and olanzapine have much greater antihistaminergic action. Side effects are a function of illness + dose + personal factors ( age, gender et) . It is difficult to answer that question as there are many variable to consider as mentioned
Ok here’s another question if you don’t mind.
I take Trazodone 50mg for sleep and that affects H1 receptors how come that doesn’t make my anxiety go crazy like seroquel zyprexa Celexa or anything that acts highly as an antihistamine?
how long does it take for a increase from 1-2 mg in rexulti take to work
The onset of action can differ from person to person. If prescribed the doctor should be able to give you details about this.
Can I take brexpiprazole 0.5mg with mirtazapine for depression and anxiety
I’m currently on 45mg mirtazapine ??
This combination can be prescribed in general. However we cannot comment on your specific situation - your prescriber is in the best position to answer that.
If aripiprazole has stopped working as well as it used to, would it be a good idea to switch to brexpiprazole or would it have the same effect of not working after a few months? (I'm a patient but am very curious to know what they will put me on next as my aripiprazole has stopped working as well as it did.)
It varies but the switch in most cases is straightforward. There are subtle differences between the two. Brexpiprazole has lower intrinsic activity as D2 agonist, increased 5HT2A antagonism & 5 HT1A partial agonist providing benefits in mood and also anti noradrenergic properties providing benefits in trauma disorders.
@@PsychiatrySimplified Thank you so much for the reply!
Thx doc! How is the comparison between brexipiprazole and cariprazine?
Good question. I’ll add this on the list. Brexpiprazole is a D2 Partial agonist. Cariprazine has greater action at D3 than D2 and is a partial agonist. I covered cariprazine in a short. You can read about this here psychscenehub.com/psychinsights/cariprazine-mechanism-of-action-psychopharmacology-clinical-application/
@@PsychiatrySimplified thanks doc.. i've read it and its great to see that u have compared it with brexipiprazole and aripiprazole in terms of weight gain, somnolence, and akathisia..
I really love how you deliver the difficult topics becoming simplified. Thx doc 🙏
Thanks for the feedback 🙏🏻
Sir, one of my close relatives, was on Olanzapine 5mg for 6 months but due to weight gain issues her psychiatrist switched her to Lurasidone 20mg abruptly, and now she has become extremely restless, irritable & agitated with insomnia, also probably a bit of tremors. Is it possible that it's due to anticholinergic/antihistaminergic rebound ? How these antipsychotics should be cross titrated ?
Olanzapine suddenly ceased can result in antihistaminergic and anticholinergic rebound. Lurasidone is associated with akathisia. Therefore cross titration should be considered with olanzapine at times maintained at very low doses to avoid rebound. Rebound plus lurasidone akathisia can be exaggerated if olanzapine is suddenly ceased. In this article towards the end strategies have been explained psychscenehub.com/psychinsights/antipsychotic-withdrawal-syndrome-tapering/
Is it possible to switch over from Aripiprazole to Brexpiprazole smoothly after being on A for more then a year?
From a pharmacokinetic perspective yes as both have long half lives . Adjustments of dose may need to be made with monitoring. This depends on individual to individual. Ps not advice.
Thankyou for the reply
Just curious-at what doses do you see patients having a response to Rexulti? 0.5mgs? 1mg? Does it take 8 weeks to see a response or a few weeks? Thank you again! Don
It depends on the condition. In the first episode of schizophreniform psychosis - 0.5-1-5mg. Higher doses are needed for more severe illnesses - the half-life is long around 90 hrs so the steady state level isn't reached until about 10-15 days later - so it is important to allow some time for a full effect - having said that, initial benefits of improved mood, sleep etc can occur earlier. In depressive psychoses - low doses of 1-2 mg are usually needed.
You explain it to doctors or people? You have to explain in simple words showing actual results on a person, not all these jumbo-mumbo terminology. You show you know your stuff, but I got no clue what's the difference.
Is Brexpiprazol available as monthly depot or 3 monthly or liquid.
Not as a long acting injection or liquid as of yet. This can change in the future and best checking with the company that manufactures the mediation or the pharmacist.
what do you mean by day 8 is 4mg? do you mean 7day +1 day you put the patient on 4 mg? can you please elaborate on that I am confused
This is recommended dosing - Day 1 - 1 mg ; Day 5-7 2 mg and increase ; by day 8 - can reach 4 mg if needed.
@@PsychiatrySimplified thanks!
Hello doc. Have you done a video on vraylar yet by chance? I just got 4 weeks worth of samples and they want me to do it every other day. Currently on Zoloft 100mg so this would be a add on for treatment resistant depression. I really prefer listening to your explanation over anyone else😊
Haven't done one yet , but have written a detailed article psychscenehub.com/psychinsights/cariprazine-mechanism-of-action-psychopharmacology-clinical-application/
@@PsychiatrySimplified thank you as always for the info! Today was day one and it wasn’t bad but wasn’t good. I’m assuming this will ease up a bit?
@@kevinherron6051 cariprazine has a very long half life so steady state level takes some time . The half life of its metabolite is around 7 days so steady state levels may take up to 3-5 weeks . Results are usually seen around 2-4 weeks. Longer than some others. However initial effects may still be present - just means that one needs a longer interval to evaluate efficacy and side effects.
@@kevinherron6051 here is a short that I did based on your request Cariprazine | Vrylar | Reagila Explained - D2/D3 Partial agonist #psychiatry #schizophrenia
ua-cam.com/users/shortsAHd3-e8gwws?feature=share
@@PsychiatrySimplified you’re the best!
You're forgetting the sexual side effects. When I was on Brexpiprazole I had uncontrollable sexual desires. Which led me to getting scammed out of $2,000 All I could think was sex. With constant erections. And with the long half life it was not fun. So what's receptor caused that doc
I've been bipolar 2 depression for 25 years. The past 5 years treatment resistant until I found trintellix 4 months ago. And got diagnosed ADHD this week. So will ADHD medicines do the same thing as this medicine did to me?...
Im sorry to hear! Yes its a side effect that occurs a lot more with Ari - what dose was it? There are warnings of Ari for pathological gambling now. This occurs due to the partial DA agonist effect - its interesting its happened with Brex as it is > antagonist - wonder if the dose was low? Thanks for the warning. With stimulants yes one should be cautious if this has happened with a dopamine partial agonist - please let ur prescriber know - as it may need cover with mood stabiliser - ps not advice. Having said that brexpiprazole can do this in the context of excessive D2 antagonism which leads to excess D1 phasic dopamine ( impulse dyscontol disorders ) - one can only know after an examination and history. Ps not advice
Does abillify cause diabetes and is this reversible on 5mg from 3 months
It has a lower incidence of metabolic dysfunction however if this occurs after starting the medication this may indicate a vulnerability and one should discuss this with their doctor .
Could you do a video on methylphenidate?
Sure we will aim to. In the meantime, you can have a read of mechanisms of action of stimulants (diagrams included) in this article psychscenehub.com/psychinsights/diagnosis-and-management-of-adult-adhd/
@@PsychiatrySimplified Thank you!
Added a separate article psychscenehub.com/psychpedia/methylphenidate-mechanism-of-action-side-effects-and-dosing/
on Wikipedia it says its the opposite of Abilify in terms of dopamine stimulation - would a stronger dose of Rexulti create more stimulation or blockage of dopamine
A higher dose may do it however by nature partial agonists have a ceiling effect - if further dopamine blockade is needed it's better to use a D2 antagonist. You can read about aripiprazole here. psychscenehub.com/psychinsights/aripiprazole-mechanism-of-action-psychopharmacology-and-clinical-application/
@@PsychiatrySimplified so a high dose of Rexulti can maybe create more stimulating effects? The partial agonist effect of abilify is basically non-existent and I want to try Rexulti for this very reason but you mention that there is a "ceiling effect" meaning a higher dose of Rexulti could diminish it's partial agonism of dopamine? Also, this is kinda off topic but I just found out that Armodafinil is a D2 partial agonist! I'm currently taking modafinil and strongly miss the partial agonist effect that Abilify used to give me
@@creativejustice1298 brexpiprazole can do - but less likely than Aripiprazole. Ceiling effect means that if D2 blockade is required one isn't going to get a linear increase in D2 blockade by increasing doses as one would with D2 antagonists:. Armodafinil is a dopamine agonist and dopamine reuptake inhibitor ( net effect increase in dopamine ) - it does not act as an antagonist with high dopamine levels ( I.e no partial agonist effect )
@@PsychiatrySimplified by partial agonist effect I'm referring to what the drug companies warn as "A strong desire to gamble, binge eat, shop, and engage in sexual activity" may occur. Those urges are from the partial stimulating effects of the D2 receptor. When I first took Abilify - I had a increase in libido because of this and I'm hoping Rexulti will do the same
@@creativejustice1298 yes partial agonists can do that. In fact aripiprazole is a treatment for AD induced sexual dysfunction.
How does brexpiprazole compare to paliperidone?
Brexpirpazole is a partial DA D2 agonist ; Paliperidone is a D2 -5HT2A antagonist. Paliperidone elevates prolactin significantly. Brex is prolactin sparing. See summary of AP here - ua-cam.com/video/3vLSMZObXqE/v-deo.html
Which would give worse akathesia paliperidone or brexpiprazole?
Been on 3mg rexulti for two years but showing high cholesterol, what should I do?
Generally rexulti metabolically friendly but best to discuss this with your doctor.
If I gained weight with abilify, will I gain weight the same with brex. ?
What dose of aripiprazole? Yes it’s a possibility because brexpiprazole has anti-histaminergic activity which can lead to weight gain. But the only way of knowing is by trialling, in such cases adding metformin in advance is an evidence based strategy to prevent weight gain. In such circumstances identifying causes is important
Does this help CFS more than Abilify then?
One can't really say. It all comes down to the symptoms. CFS is not a single entity. It has multiple symptoms. So the question is what Sx is one trying to treat. In most severe cases of CFS there is no single Rx that treats all Sx because the condition is multifactorial.
@@PsychiatrySimplified thank you. I wish you were in the us. Mine is severe. It’s awful. Awful doesn’t describe it even. Have you heard of clients with cfs feeling like they are being pulled down to the ground, like a sense of vertigo but it goes with all the other symptoms .. it’s not just vertigo… may be related to the blood flow issue .. it eventually can lead into the major fatigue. Only benzos help it some. Would that mean it is coming from anxiety?
Abilify really caused me to not be able to move as i crashed badlu after taking it. Does it cause less tiredness that abilify? I only took .25 mg then onlu took 1/10 of that and crashed immediately.
@@PsychiatrySimplified
What if the symptoms is feeling loss of control of your brain and focus and thay then leads into the fatigue. Something needs to calm this out of control brain .. as this happens it comes with a vertigo pulling feeling down as you sink into the fatigue and lack of brain functionality . Benzos have helped tbis down for me in the past. I don’t know what else to try
How long does it take to work in low dose for cfs or those who don’t have schizophrenia? And how long for the tiredness part to go away? I can’t do more fatigue.
Can you take with benxodiazapines?
Which causes least amount of weight gain
Some of the typicals haloperidol but have other side effects. Newer agents like ziprasidone, lurasidone, aripiprazole, brexpiprazole, cariprazine are metabolically friendly but other side effects should be weighed up.
What differences between Aripiprazole and Brexpiprazole?
the differences between aripiprazole and brexpiprazole are covered in the video. Aripiprazole has higher intrinsic activity at the D2 receptor and acts as an antagonist at clinically relevant doses with brexpiprazole less so. Brexpiprazole, therefore, has a better side effect profile. Brexpiprazole also has 5HT-7 and alpha 2 antagonism providing pro-cognitive effects and antidepressant effects. psychscenehub.com/video/brexpiprazole-psychopharmacology-side-effects-and-clinical-pearls/
@@PsychiatrySimplified thanks, I take Solian, doctor wants to switch to Abilify, and I was wondering if Rexulti would be better or not than Abllify or Solian.
I don't know wich one of the three would be more efficient.
@@user-lb1bh4df6b Hi PS: Can't give medical advice. It depends on the symptoms that are being treated. Solian (Amisulpride) is a D2/D3 antagonist - at lower doses acts as D3 antagonist (antidepressant properties and against negative symptoms of schizophrenia) - higher doses (antipsychotic effect with increased prolactin as a potential side effect) Brexpiprazole and Aripiprazole are prolactin sparing and are partial agonists - very different to solian. Have a look at this simplified guide to antipsychotics psychscenehub.com/psychinsights/a-simplified-guide-to-antipsychotic-medications/
Amisulpride - D2/D3 antagonist
It preferentially blocks pre-synaptic D2/D3 dopamine receptors, producing dopamine release responsible for its disinhibitory effects. This atypical pharmacological profile may explain amisulpride’s antipsychotic effect at higher doses through post-synaptic dopamine receptor blockade located in the limbic areas and its efficacy against negative symptoms, at lower doses, through presynaptic dopamine receptor blockade.
In addition, the reduced tendency of amisulpride to produce extrapyramidal side effects may be related to its preferential limbic activity
Dose 400 mg - 1200mg / day
Dose dependant QTc prolongation
Prolactin elevation and EPSEs due to post-synaptic dopamine blockade
@@PsychiatrySimplified thank you.
I take 100mg a day against depression and negative symptoms of schizophrenia.
I'm going to read this article right now, thanks 👍
Is taking Aripiprazole 2.5 mg daily causes weight gain and Diabetes. Plz reply.
Low risk of both but in some individuals it can - so it's not an absolute
Thanks Sir
@@neetusharma198Check out your carb intake and switch to higher gi foods like carrots apples and whole grain pasta this will likely fix the cholesterol and hyperglycemia issues associated with aripripazole
why don't you explain what antagonist and agonist mean?
Thanks for bringing that up. Agonist - activates receptors / antagonist - blocks receptor and hence 👇neurotransmitter activity
Y'know, I'm a little annoyed by this 'goldilocks zone,' 'optimization,' and agonists 'raising and lowering the levels of neurotransmitters' language.
As you know, the levels of monoamines are not changed by the ligands (directly; excepting effects on autoreceptors, perhaps, it depends on what one means by 'directly'), so it's misleading to talk about them that way; unless we're talking about displacement from another site on the complex, dopamine levels don't really have anything to do with this at all. And the switching of the g-protein is binary, so it's not really about more or less of an effect, it's about the probability of any given GPCR in a population being activated at equilibrium in a sufficiently large population of neurons.
The goldilocks bit is wrong in two ways; not only is there no way to know whether the efficacy (depending on the source) of brex or aripiprazole is 'optimal', but the activation of any given receptor is random - it's just that the number of activations in a population changes at equilibrium depending on efficacy of the ligand. So maybe it's a 'goldilocks zone' or 'less dim room' for populations of neurons, but it's not about neurotransmitters or individual synapses at all, which is kind of what your wording suggests.
I'm concerned that in the attempt to make things comprehensible to audiences, much of the science gets abandoned in favor of cozy metaphors, which feels kind of patronizing to anyone with a bit of science background, and makes one worry a bit if doctors themselves even know the science.
For the YT channel it is simplified . But for medical purposes written about it here. The principle is that it acts as an agonist in context of low endogenous dopamine and antagonist at higher levels of dopamine. So the dimmer switch or goldilocks is to highlight the modulation rather than an actual change in levels of neurotransmitters. Conceptually however it’s easier to explain : and clinically also very testable . In other words it’s acts as an antagonist as if the dopamine levels were reduced without actually reducing them. But you raise an important point. psychscenehub.com/psychinsights/brexpiprazole-psychopharmacology/
@@PsychiatrySimplified
I think that's even kind of a cozy oversimplification at its core. There are differential effects on different DAr subtypes, but I have yet to have someone explain to me how the drug 'knows' how to act in this corrective capacity.
It seems simpler to just say that it has a constitutive activity of some kind, and that's going to be higher than the basal DA activity in some places, and lower in others. So it brings, at the high level of occupancy typical with these drugs, the number of D2r activated cells closer to a particular average.
I may be missing something here, but I haven't been able to find any direct evidence of this claim, unless there's some kind of complex equilibrium with dopamine... but that doesn't really make sense, since if that were the case it would be displaced at high concentrations
@@eligalilei204 not sure why it’s oversimplification ? They have very strong affinity for DA receptors - intrinsic activity can be modulated which is what they have done - Brexpiprazole 25 % lower intrinsic activity than aripiprazole . In clinical practice the dose modulation is needed to manage symptoms. But in development they have been able to look at affinity at different doses and intrinsic activity. This varies however based on endogenous DA levels.
@@PsychiatrySimplified
It's the claim that it acts differently based on the amount of monoamines present that seems questionable, or at least not understood by me.
The drug has different affinities to different subtypes, but the same receptor conformation is induced when seated in the pocket; that's not dependent on the amount of monoamines present. Sure, it's less activity than the endogenous agonist induces (less likelihood of activation), and more likely to activate than if there was no dopamine present.... but the dependence on DA levels claim seems like a convoluted way to hype up partial agonism.
Again, maybe I'm missing something and should just review the literature once more.
There is an additional kink added by the partial agonism at autoreceptors, but that would actually reduce levels when they're low, and increase them when high, which is another issue entirely.
Perfect 👌