serotonin-dopamine activity modulator (SDAM)?

[asecin]

i just found out about this drug named Brexpiprazole, which is considered advanced new antipsychotic with possible applications for major depressive disorder. it was just approved by FDA last year, its very new drug and likely not many tried it at all, considering probable very high cost as of yet too. but i got really curious about this term serotonin-dopamine activity modulator (SDAM) ive never seen this being used for any other drug before. my main interest is for its depression effect and how this might play out. anyone with some knowledge and understanding about this new drug's mechanism care to elaborate on its likehood of helping depression beyond just its action as new antipsychotic, please share!

 

[Ligaturd]

Well. I just learned of this chem as well when searching for the medication I just started, aripiprazole (abilify). Its manufactured by the same pharmaceutical company and according to wiki had similar activity as a partial (inverse agonist) but more of an antagonist than an agonist whereas aripiprazole functioned as more of an agonist at sites like D2 and D3. From what I understand this makes brexpiprazole more likely to cause prolactin increase and typical anti-psychotic side effects than it's predecessor, aripiprazole.

Aripiprazole is already used in conjunction with SSRI's and SNRI's when these meds just aren't doing much to help with major depressive disorder so you can probably get a glimpse of how brexpiprazole will work for these purposes based off of that. Being an inverse agonist seems to make peoples reactions to these medications vary quite wildly based on the person and the dosage.

Aripiprazole can actually increase mania and psychotic symptoms if it works more like an agonist than an antagonist in some people. Stimulating D2 and D3 and increasing impulsivity, sexual appetite and... Well you get the picture.

 

[asecin]

so its likely to just be like taking aripiprazole with SSRIs and SNRIs. thats not such a huge advacement BUT it will compensate you instead of taking several pills at once :/

 

[Nagelfar]

This made me think of Vortioxetine (a so called Serotonin modulator and stimulator (SMS)) when it comes to new drug, with agonism, and antagonism, etc. Much like "serotonin-dopamine activity modulator (SDAM)" it seems to be a new name just tagged on that isn't really anything much different than a lot of other drugs.

 

[Ligaturd]

Well, aripiprazole and brexpiprazole act as partial agonists at D2, D3, 5ht1a, 5ht2C. So, as anti-psychotics they are fairly unique. Some people receive more stimulation than antagonism at these sites so it could possibly be counter productive, especially when antagonism is typically what is called for. Some people experience worsened symptoms and things such as gambling addiction and sex addiction. I believe one man won a case against this pharmaceutical company because he claimed that abilify MADE him into a dirty little butt slut and he started having risky gay sex while married. I don't think drugs can turn people gay but he set a precedent there lol.

So for some people. it could be helpful for artificially raising dopaminergic and serotonergic activity at these sites and there could be some benefit. I think aripiprazole would serve this purpose better though as brexpiprazole is more of an antagonist as I previously mentioned.

https://en.wikipedia.org/wiki/RP-5063

this one seems interesting. It seems like other pharmaceutical companies are trying to develop more anti-psychotics that are mixed agonist antagonists

 

[asecin]

heh " "dopamine-serotonin system stabilizer" sounds so enticing!

ligaturd since you started aripiprazole what do you have to report on it, both positive-negative etc? do you really think an actual antipsychotic like this one can raise dopamine and serotonin "stabilize" even and be of benefit for people with depression?
because i have low density expression D2 based on gene test, and it says to stay away from antipsychotics, but in the case of this one, is it a good option to raise dopamine specifically in my case?

 

[aced126]

Well. I just learned of this chem as well when searching for the medication I just started, aripiprazole (abilify). Its manufactured by the same pharmaceutical company and according to wiki had similar activity as a partial (inverse agonist) but more of an antagonist than an agonist whereas aripiprazole functioned as more of an agonist at sites like D2 and D3. From what I understand this makes brexpiprazole more likely to cause prolactin increase and typical anti-psychotic side effects than it's predecessor, aripiprazole.

Aripiprazole is already used in conjunction with SSRI's and SNRI's when these meds just aren't doing much to help with major depressive disorder so you can probably get a glimpse of how brexpiprazole will work for these purposes based off of that. Being an inverse agonist seems to make peoples reactions to these medications vary quite wildly based on the person and the dosage.

Aripiprazole can actually increase mania and psychotic symptoms if it works more like an agonist than an antagonist in some people. Stimulating D2 and D3 and increasing impulsivity, sexual appetite and... Well you get the picture.

If people who were psychotic and put on a D2 inverse agonist then went on to become impulsive, I'd say that provides more evidence that there are other significant receptors involved in schizophrenia.

 

[Jabberwocky]

heh " "dopamine-serotonin system stabilizer" sounds so enticing!

ligaturd since you started aripiprazole what do you have to report on it, both positive-negative etc? do you really think an actual antipsychotic like this one can raise dopamine and serotonin "stabilize" even and be of benefit for people with depression?
because i have low density expression D2 based on gene test, and it says to stay away from antipsychotics, but in the case of this one, is it a good option to raise dopamine specifically in my case?

It's called Brahmi or Bacopa Monnieri -- been used for thousands of years

Upregulates Downregulated 5HT receptors and vice versa
Upregulates Downregulated DA receptors and vice versa
Upregulates Downregulated GABA (A&B) receptors and vice versa

There are lots of citations -- I'm not posting them all

 

[asecin]

shugenja i was using that crap for a while in hope to relieve some depression but i never felt it or perhaps i did and it wasnt positive. thanks tho, always appreciated when the herbal guy joins the convo and tries to contribute

 

[Ligaturd]

heh " "dopamine-serotonin system stabilizer" sounds so enticing!

ligaturd since you started aripiprazole what do you have to report on it, both positive-negative etc? do you really think an actual antipsychotic like this one can raise dopamine and serotonin "stabilize" even and be of benefit for people with depression?
because i have low density expression D2 based on gene test, and it says to stay away from antipsychotics, but in the case of this one, is it a good option to raise dopamine specifically in my case?

Its hard to say either way. People react to various doses in vastly different ways. On 2mg I couldn't stay awake and it's supposed to be stimulating, I tried 5mgs and it was stimulating. So, it's far too early to tell for me. It's been about a week. I don't have any horrible side effects as of right now and I sincerely hope it stays that way because traditional anti-psychotics have side effects that just don't agree with me.

I have read anecdotal reports that it's supposed to regulate dopaminergic and serotonergic activity, tipping the scale one way or the other based on either excess endogenous activity or vice versa, that is what is responsible for the wide variety of responses from patients apparently.

I have absolutely nothing bad to report as of right now but it will be a month or so until I have a better understanding of how it affects me. I was getting gynecomastia from olanzapine which is a full antagonist at D3 which causes prolactin levels to increase. This lowers sex drive and causes breast tissue formation. Not something one wants to have to go through when they are trying to get their life together lol. Aripiprazole being a partial agonist at D3 actually lowers prolactin levels and acts as a cure for gynecomastia. I'm really hoping this is the right anti-psychotic for me.

People have varying levels of success with it but it is approved for use in the way that you mention. It is definitely worth talking to a doctor about and maybe trying. My depression seems to have leveled off since taking it but as I've mentioned, it's much too early to tell anything for certain.

 

[Jabberwocky]

shugenja i was using that crap for a while in hope to relieve some depression but i never felt it or perhaps i did and it wasnt positive. thanks tho, always appreciated when the herbal guy joins the convo and tries to contribute

It takes a minimum of 12 weeks for any type of response to occur in humans (based on literature) -- furthermore, the concentration of bacosides needed are much higher than the recommended dosage

Not really an herbal guy, but I do recognize that an herb that has been used in Ayurvedic medicine for 5000 years, and which mechanism of action has been confirmed with in vivo studies in human subjects -- may be efficacious

 

[palmanita]

I don't like that this atypical antipsychotic (it's one, isn't it?) is more towards antagonism than agonism. We have more than enough of them, but basically no selective dopamine partial agonists, selective serotonin ant/agonists etc ...

Let's call O-PCM a glutamate activity modulator (GAM)!

 

[Ligaturd]

Aripiprazole is actually more towards agonism than antagonism in many people. Brexpiprazole is more towards antagonism than agonism apparently. But from what I read they apparently don't fully understand the mechanisms at play here. They have somewhat of an understanding of how they work but a lot of it is just assumptions based on apparent cause and effect.

Some people receive an increase in mania and hallucinations from Abilify suggesting that it has more agonistic activity than antagonistic. Just surfing through wikipedia you can see chemicals in development that are playing around with partial agonism. It's actually refreshing to see that there is at least some innovation in atypical anti-psychotics. Aripiprazole doesn't posess many of the side effects (to the same degree) that have been a staple of neuroleptics since their beginning. These chems are partial agonists for dopamine and serotonin receptors and many are in development as we speak.