![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 20 of 20. This is the beginning of the thread.
Posted by jay2112 on June 3, 2021, at 18:41:39
I sort of have a hard time grasping the fullness of this article. Next gen of antipsychotics?
Posted by undopaminergic on June 4, 2021, at 7:42:19
In reply to Can some of you sci wizs explain..next gen ap's, posted by jay2112 on June 3, 2021, at 18:41:39
> I sort of have a hard time grasping the fullness of this article. Next gen of antipsychotics?
>
> https://www.nature.com/articles/d41586-018-02328-zIt's about the structure of dopamine D2-receptors and the possibility of designing drugs that are selective for this receptor.
-undopaminergic
Posted by alexandra_k on June 7, 2021, at 13:27:07
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by undopaminergic on June 4, 2021, at 7:42:19
> It's about the structure of dopamine D2-receptors and the possibility of designing drugs that are selective for this receptor.
Yep
Posted by Lamdage22 on June 8, 2021, at 1:07:52
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by alexandra_k on June 7, 2021, at 13:27:07
What are the advantages of that? No weight gain?
> > It's about the structure of dopamine D2-receptors and the possibility of designing drugs that are selective for this receptor.
>
> Yep
>
>
Posted by undopaminergic on June 8, 2021, at 5:37:50
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by Lamdage22 on June 8, 2021, at 1:07:52
I don't know, but possibly less potential of worsening of negative symptoms.
-undopaminergic
> What are the advantages of that? No weight gain?
>
> > > It's about the structure of dopamine D2-receptors and the possibility of designing drugs that are selective for this receptor.
> >
> > Yep
> >
> >
>
>
Posted by SLS on June 8, 2021, at 10:26:08
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by undopaminergic on June 4, 2021, at 7:42:19
I think the key with these drugs is that they don't spend very much time attached to the D2 receptor. They hop on and hop off quickly. My guess is that this minimizes dopamine receptor supersensitivity, and thus reduces EPS. The features of the D2R include pieces of the receptor sticking out of the membrane and the formation of pockets within the receptor. The proposed antipsychotics are attracted to these pockets, which don't exist on any other type of dopamine receptor. This effectively makes these drugs not only selective, but perhaps even *specific* to D2R. The other dopamine receptors don't seem to be involved with the therapeutic effects of existing antipsychotics.
- Scott
Posted by alexandra_k on June 8, 2021, at 18:16:31
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by SLS on June 8, 2021, at 10:26:08
They did say that they have reason to believe the dopamine receptor to be involved in the positive symptoms (e.g., delusions, hallucinations, intense affective responses) rather than the negative symptoms (e.g., social withdrawal). So focusing on a particular kind of dopamine receptor is only likely to help with the positive symptoms rather than the negative.
So not a revolutionary medication. But incrementally better.
Long-term anti-psychotic use has been implicated in tardive dyskinesias (tremors and movement disorder) or Parkinson's (like) movement symptoms. Facial twitching etc. I think that is true for the new generation anti-psychotics also. The risk is less with new than the old generation anti-psychotics, but I think the risk is still there, it just takes heftier doses of the newer generation medicines over a longer period of time because the medications are more specific. The hope is that this will be the next generation of specificity.
The hope of a more specific medication is that there will be a stronger response for less of a dose. So people who are on the maximum dose their bodies can tolerate (because of side-effects like drooling or extreme lethargy or sun sensitivity etc) may be able to have the dose increased without an increase in side-effects for greater therapeutic benefit. Or, they may be able to maintain the therapeutic benefit with less of a dose of the medication. Which would mean less likelihood of long term use of dopamine medications.
It can be hard to disentangle negative symptoms from side-effects of medications IMHO. But I don't have a lot of experience so maybe that is not true to trained clinicians... But I think that a lot of what people think or believe to be negative symptoms are actually side-effects from medications it is just that the benefits are thought to outweigh the harms and when people are worried about acute emergencies they aren't thinking or worrying so much about longer term issues.
Posted by SLS on June 8, 2021, at 20:36:26
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by alexandra_k on June 8, 2021, at 18:16:31
> They did say that they have reason to believe the dopamine receptor to be involved in the positive symptoms (e.g., delusions, hallucinations, intense affective responses) rather than the negative symptoms (e.g., social withdrawal). So focusing on a particular kind of dopamine receptor is only likely to help with the positive symptoms rather than the negative.
Alexandra, nobody said that risperidone and other antipsychotics didn't have other properties that address negative symptoms - probably 5-HT2a antagonism. However, it is not necessary to block any other type of dopamine receptor other than the D2R to reduce positive symptoms.
The salient point of the article is that you can build an antipsychotic with significantly less liability to produce EPS, yet retain antipsychotic activity. That's all. For some people, this might be incrementally better, but that might be one hell of an increment. We'll see.
Let the doctors and the sufferers decide for themselves whether taking one of these D2R-specific drugs represents something revolutionary or not. How would you evaluate the statistical rate of EPS of these new drugs compared to the older ones? Would you consider it revolutionary to stamp out EPS, TD, and NMS? I would.
If you can find the results of clinical trials examining EPS in these new antipsychotics, it would be great if you could post links to them.
I sometimes have emotional attachments to my guesses, but I prefer to let science come to conclusions - and even then, there is no guarantee that the truth will have been ascertained.
- Scott
Posted by alexandra_k on June 10, 2021, at 3:11:37
In reply to Re: Can some of you sci wizs explain..next gen ap's » alexandra_k, posted by SLS on June 8, 2021, at 20:36:26
Yes, fair enough. I hear you on the 'revolutionary' point. Also that there may be other things to help with negative symptoms in the medications.
Posted by SLS on June 10, 2021, at 15:59:16
In reply to Re: Can some of you sci wizs explain..next gen ap's » SLS, posted by alexandra_k on June 10, 2021, at 3:11:37
> Yes, fair enough. I hear you on the 'revolutionary' point. Also that there may be other things to help with negative symptoms in the medications.
Well, there have been so many disappointments in the past. That's for sure.
I was hoping that Abilify or Vraylar would help with negative symptoms. Even Latuda would be worth looking at. Guesses only. Again, the idea with the newer D2 specific antagonists is that EPS might be much reduced. I don't really know the armament used to treat schizophrenia.
It's too bad that amisulpride isn't available in the U.S. According to what I just read, it might be the best antipsychotic for negative symptoms.
- Scott
Posted by Christ_empowered on June 10, 2021, at 21:57:45
In reply to Re: Can some of you sci wizs explain..next gen ap's » alexandra_k, posted by SLS on June 10, 2021, at 15:59:16
i dunno. I'm thankful that I can take (now generic...still ridiculously over-priced, somehow...) Abilify instead of...well, in my case, just about anything else.
it isn't that Abilify is a miracle pill, its just...less mind numbing, the research I've skimmed on it would seem to indicate it may be less toxic (fewer cardio deaths, less sedation, maybe less cognitive impairment) than just about anything else that's out there or at least...
out there and available to -me- , an increasingly disillusioned "mental health consumer."
so...progress is always much appreciated, most definitely. if not for me, personally, then definitely for the next generation of the mentally destroyed.
I kind of doubt much will help "negative symptoms." not saying that to be a Bummer Bob, just...a lot of what the experts choose to call "negative symptoms" is: a result of the drugs, a result of social isolation, a result of considerable stigma which often exacerbates social isolation, and...wait for it, wait for it...poverty.
its worth noting that the severely mentally ill tend to die about 15 years earlier than others in many EU nations. I think in the US the gap is worse, 20 or 25 years. and...
true to form, the antipsychiatry people point to the pills, the periodic confinement to explain this. which, honestly, is not a bad explanation, especially since the 'atypicals' carry -serious- metabolic risks that are not found with, say, moderately dosed phenothiazines.
personally, I think the pills are part of the problem. the poverty, to me, is probably a better explanation. why is one labeled with schizophrenia? poor. why is one prescribed toxic cocktails? poverty. why is one denied adequate health care? poverty.
no magic pill for poverty, I'm afraid. :-(
Posted by Lamdage22 on June 11, 2021, at 1:10:57
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by Christ_empowered on June 10, 2021, at 21:57:45
I think they often are. Overused. They mask the problem and don't even touch the root cause. Foreign humanmade substances that the body doesn't appreciate at all. I would say, unless you are in a violent or suicidal rage, get your nutrients straight and do psychotherapy. If you are in a rage of these sorts, do the same and take something to calm you ontop of that. Then see if you can wein off with the help of psychotherapy and nutrients you are deficient in.
These are just my two cents that no one seems to appreciate here. Its okay. I accept it. I am accepted and not attacked for my views, too, so the least I can do is the same for those that have opposite views. I think it works ok.
I would get extensive bloodwork BEFORE taking foreign chemicals, unless you are REALLY out of it. It also depends wether or not you are in a hospital. They can keep you from doing anything stupid. When you are at home, they cannot.
> personally, I think the pills are part of the problem.
Posted by Lamdage22 on June 11, 2021, at 1:18:42
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by Lamdage22 on June 11, 2021, at 1:10:57
Clearly, I'm not suggesting that anybody mindlessly come off their drugs that they are already on though. Please don't get that wrong.
Posted by alexandra_k on June 11, 2021, at 3:54:10
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by Lamdage22 on June 11, 2021, at 1:18:42
they still over-prescribe old generation anti-psychotics in these parts. when chlorpromazine was first invented they hailed it as a 'chemical straightjacket'. they thought that chemical induction of... immobility. stupor. was more humane, somehow, than physically restraining people. in other words, they use it intentionally to mind-numb people into a stupor or Catania or depression sort of immobilised slumber in these parts. they get money for having them. in hospitals. in aged care facilities. they get money for having them. and the medications are cheap. and they don't have to pay them a living wage etc. so... poverty. etc. yeah.
Posted by SLS on June 12, 2021, at 10:57:13
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by Christ_empowered on June 10, 2021, at 21:57:45
Hi, C_E
> personally, I think the pills are part of the problem. the poverty, to me, is probably a better explanation. why is one labeled with schizophrenia? poor. why is one prescribed toxic cocktails? poverty. why is one denied adequate health care? poverty.
>
> no magic pill for poverty, I'm afraid. :-(Tell me about it.
- Scott
Posted by SLS on June 12, 2021, at 11:01:10
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by Lamdage22 on June 11, 2021, at 1:10:57
Hi.
> > personally, I think the pills are part of the problem.
In what ways? I agree that this is true in for a great many people. But I'm curious about the details that motivated you to say that.
Thanks.
- Scott
Posted by Lamdage22 on June 13, 2021, at 0:28:04
In reply to Re: Can some of you sci wizs explain..next gen ap's » Lamdage22, posted by SLS on June 12, 2021, at 11:01:10
C_E said that.
> Hi.
>
> > > personally, I think the pills are part of the problem.
>
> In what ways? I agree that this is true in for a great many people. But I'm curious about the details that motivated you to say that.
>
> Thanks.
>
>
> - Scott
>
>
Posted by SLS on June 13, 2021, at 13:56:05
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by Lamdage22 on June 13, 2021, at 0:28:04
> C_E said that.
Sorry. My bad. Thanks for setting me straight.
- Scott
>
> > Hi.
> >
> > > > personally, I think the pills are part of the problem.
> >
> > In what ways? I agree that this is true in for a great many people. But I'm curious about the details that motivated you to say that.
> >
> > Thanks.
> >
> >
> > - Scott
> >
> >
>
>
Posted by Lamdage22 on June 13, 2021, at 15:15:57
In reply to Re: Can some of you sci wizs explain..next gen ap's » Lamdage22, posted by SLS on June 13, 2021, at 13:56:05
I'm not to keen on setting people straight but I'm sure nothing was said to cause harm.
Posted by SLS on June 18, 2021, at 20:46:49
In reply to Re: Can some of you sci wizs explain..next gen ap's, posted by Lamdage22 on June 13, 2021, at 15:15:57
> I'm not to keen on setting people straight but I'm sure nothing was said to cause harm.
Yeah. Not the best choice of words.
- Scott
This is the end of the thread.
Psycho-Babble Medication | 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.