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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 23 of 23. This is the beginning of the thread.
Posted by Quintal on March 4, 2008, at 11:15:46
I went to my pdoc appointment today and he gave me amisulpride 50mg for depression. I think he was itching to give me a higher dose - I was on 200mg in hospital, but I explained that as little as 25mg helps and more than 50mg makes me too agitated so he agreed. I have to go back to my GP for zopiclone though because he doesn't want two doctors giving me it at the same time. I made an appointment for tomorrow so we'll see how that goes, but I have no hope. I may have to get my social worker to force her on Thursday if needs be.
I took my first dose less than an hour ago, and as usual it had an instant 'mood-brightening'/pro-social/dopamine rush effect. I might actualy be able to get on with all the things I want to do now without it feeling like torture.
Q
Posted by bleauberry on March 4, 2008, at 16:31:23
In reply to Amisulpride, posted by Quintal on March 4, 2008, at 11:15:46
The first time I ever tried amisulpride I got that same dopamine rush kind of feeling and it was like instant antidepressant. As with anything dopaminergic, that feeling built tolerance and faded in days. With continued use however it had time to do more a true therapeutic effect, which resulted in more interest and motivaton, good social comfort, and just overall feeling better. Unfortunately the increaed prolactin made sex impossible.
I tried it again last year and didn't feel much for the first couple days. The third day I heard a song and I realized I just had to cry. I was so sad. I was getting a lot more depressed. It was so weird. 10 years, a ton of drugs, and mercury/lead toxicity, had changed a lot of things in that time.
I still have some onhand though and sometimes contemplate trying it again. Overall I think amisulpride has real good potential in two areas: Where someone does poorly on serotonin meds; and where someone is ok with serotonin meds but has the flat effect.
Posted by Quintal on March 4, 2008, at 18:21:48
In reply to Re: Amisulpride, posted by bleauberry on March 4, 2008, at 16:31:23
Yes, it is a good drug isn't it? I've just been looking at the wiki article and apparently it binds to the GHB receptor (incidentally I just found an old packet under the stairs last week, but it had gone soft and mushy - or else it would have solved my sleeping problems). I would presume this means it has some effect on GABA?
>I still have some onhand though and sometimes contemplate trying it again. Overall I think amisulpride has real good potential in two areas: Where someone does poorly on serotonin meds; and where someone is ok with serotonin meds but has the flat effect.
I have flat affect, to the point where it could be classified as part of the negative symptoms of Schizophrenia. So obviously amisulpride helps on that front too. It seems to be making me a little bit psychotic. I kept bursting out laughing for no partcular reason in the shop earlier tonight. I think people noticed too. Still, I would rather be that way than feeling half-dead, as with some of the other APs.
Q
Posted by bleauberry on March 5, 2008, at 18:48:27
In reply to Re: Amisulpride, posted by Quintal on March 4, 2008, at 18:21:48
Last time I tried amisulpride it was making me kind of psychotic too. I was on the back porch in the dark having a cig and I swear I was scared of the shadows. It was strange. I was feeling free floating fear of things in the dark I couldn't see. I do honestly believe that kind of feeling would resolve on its own into calmness once the receptors regulate to the new levels of dopamine. I would guess maybe a week to two.
I have not seen any literature on binding to other receptors. So I don't know about the GHB or GABA or whatever. I'm sure there is always interplay with other circuits through a downstream effect, but I don't know about the direct binding.
> I have flat affect, to the point where it could be classified as part of the negative symptoms of Schizophrenia. So obviously amisulpride helps on that front too. It seems to be making me a little bit psychotic. I kept bursting out laughing for no partcular reason in the shop earlier tonight. I think people noticed too. Still, I would rather be that way than feeling half-dead, as with some of the other APs.
>
> Q
Posted by amigan on March 12, 2008, at 21:25:55
In reply to Re: Amisulpride, posted by bleauberry on March 4, 2008, at 16:31:23
I know that i'm going a little of topic, but i'm taking Sulpride (at low dosage too) because it's a lot cheaper and never felt this dopamine rush effect.
Has any of you tried Sulpiride? How does it feel in comparision to Amisulpride?
Do you think that Amisulpride is a more potent "mood brightening" drug or not?
Posted by Quintal on March 13, 2008, at 10:14:06
In reply to Re: Amisulpride, posted by amigan on March 12, 2008, at 21:25:55
I've never taken sulprirde so I can't compare it. Amisulpride is more potent than sulpiride, but I don't really know if this translates into a more potent mood-brightening effect. I'm into my second week on amisulpride and the 'dopamine rush' effect has faded now anyway.
Q
Posted by Dopamine123 on March 14, 2008, at 16:41:58
In reply to Re: Amisulpride, posted by Quintal on March 13, 2008, at 10:14:06
I think amisulpride is usually considered to be a more effective antidepressant than sulpride, but they both have a similar mode of action.
>never felt this dopamine rush effect.
Some people won't ever feel that dopamine rush. Everyones brain is different. I think it all depends on how much activation your dopaminergic receptors get in response to the drug and whether they are downregulated too much.
Posted by Sigismund on March 15, 2008, at 3:19:58
In reply to Re: Amisulpride, posted by Dopamine123 on March 14, 2008, at 16:41:58
Does this imply that low dose amisulpride could be used episodically as a mood brightener?
Posted by Quintal on March 15, 2008, at 11:22:53
In reply to Re: Amisulpride, posted by Sigismund on March 15, 2008, at 3:19:58
That's how I'm using it now actually - as a p.r.n mood brightener for when I need a lift. I don't want to take it every day. Probably one of the few antidepressants you could use like that. Funny we both had the same idea at the same time.
Q
Posted by undopaminergic on March 19, 2008, at 11:20:57
In reply to Re: Amisulpride, posted by amigan on March 12, 2008, at 21:25:55
> I know that i'm going a little of topic, but i'm taking Sulpride (at low dosage too) because it's a lot cheaper and never felt this dopamine rush effect.
> Has any of you tried Sulpiride? How does it feel in comparision to Amisulpride?
> Do you think that Amisulpride is a more potent "mood brightening" drug or not?My interpretation of the facts is that the main pharmacological difference between sulpiride (SULP) and amisulpride (AMI) is that the latter is longer-lasting: AMI is typically taken once daily, and SULP up to three times daily. Of course, there may be slight differences in binding affinities for receptors, but the main feature of both is the high degree of selectivity for D2-like dopamine receptors (D2 > D3 >> D4). Unlike the other - "dirty" - anti-psychotics (haloperidol, risperidone, olanzapine, etc.), SULP and AMI do not block dopamine D1-like, adrenergic, serotonergic, histaminergic or cholinergic receptors. The feature (which may be shared with pimozide) that makes them uniquely effective for the treatment of dysthymia and atypical depression is their preferential affinity for presynaptic dopamine autoreceptors, the blockade of which enhances the release of neurotransmitter and results in a (somewhat paradoxical) stimulant effect on dopaminergic neurotransmission - as long as the dose is low enough not to result in extensive blockade of postsynaptic receptors. At higher doses - which may be necessary for the treament of psychosis - many of the side-effects so familiar from dirtier antipsychotics (including sedation, weight gain and motor impairments) tend to emerge.
I've tried both SULP and AMI, but it's only with the former that I've had the opportunity to experience the "dopamine rush" - a stimulant effect that beats methylphenidate (including high doses) by a wide margin in my experience.
As others have noticed, tolerance develops. It's my experience that selegiline helps reverse it, and that after approximately a week of selegiline (10 mg/day p.o.) abstinence from dopamine autoreceptor antagonists, a prominent stimulant response is again possible upon resuming the antagonist. I intend to attempt to verify that assumption in a few days.
Furthermore, when selegiline is used in combination with SULP (and presumably AMI), it potentiates the effect of the latter, and allows a longer period of chronic use before all effect is lost (or at least becomes negligible).
In theory, SULP (and thus probably AMI) potentiates the effects of cocaine (and by extension presumably methylphenidate), but I didn't notice that in practice.
Unlike some others, I haven't noticed a pronounced effect on blunted affect.
Posted by Amigan on March 19, 2008, at 14:16:04
In reply to Re: Amisulpride - and sulpiride, posted by undopaminergic on March 19, 2008, at 11:20:57
Thank you for this post.
> > I know that i'm going a little of topic, but i'm taking Sulpride (at low dosage too) because it's a lot cheaper and never felt this dopamine rush effect.
> > Has any of you tried Sulpiride? How does it feel in comparision to Amisulpride?
> > Do you think that Amisulpride is a more potent "mood brightening" drug or not?
>
> My interpretation of the facts is that the main pharmacological difference between sulpiride (SULP) and amisulpride (AMI) is that the latter is longer-lasting: AMI is typically taken once daily, and SULP up to three times daily. Of course, there may be slight differences in binding affinities for receptors, but the main feature of both is the high degree of selectivity for D2-like dopamine receptors (D2 > D3 >> D4). Unlike the other - "dirty" - anti-psychotics (haloperidol, risperidone, olanzapine, etc.), SULP and AMI do not block dopamine D1-like, adrenergic, serotonergic, histaminergic or cholinergic receptors. The feature (which may be shared with pimozide) that makes them uniquely effective for the treatment of dysthymia and atypical depression is their preferential affinity for presynaptic dopamine autoreceptors, the blockade of which enhances the release of neurotransmitter and results in a (somewhat paradoxical) stimulant effect on dopaminergic neurotransmission - as long as the dose is low enough not to result in extensive blockade of postsynaptic receptors. At higher doses - which may be necessary for the treament of psychosis - many of the side-effects so familiar from dirtier antipsychotics (including sedation, weight gain and motor impairments) tend to emerge.
>
> I've tried both SULP and AMI, but it's only with the former that I've had the opportunity to experience the "dopamine rush" - a stimulant effect that beats methylphenidate (including high doses) by a wide margin in my experience.
That's exactly what i needed to know. No "dopamine rush" with Sulp, while you experienced a notable effect with Ami. Interesting!! Maybe Amisulpride worths its money afterall.
But this also suggests that their main pharmacological difference might be something more than the half-life, as you first suggested.
> As others have noticed, tolerance develops. It's my experience that selegiline helps reverse it, and that after approximately a week of selegiline (10 mg/day p.o.) abstinence from dopamine autoreceptor antagonists, a prominent stimulant response is again possible upon resuming the antagonist. I intend to attempt to verify that assumption in a few days.
>
> Furthermore, when selegiline is used in combination with SULP (and presumably AMI), it potentiates the effect of the latter, and allows a longer period of chronic use before all effect is lost (or at least becomes negligible).
You know.. interestingly enough, i'm following the same therapeutic regime as we speak!: 10-15mg of oral Selegiline which i augment with ~35mg of Sulpiride as i was adviced to do in this thread: (Actually the suggestion was about Amisulpiride, but i went for Sulpiride because it's much cheaper)
http://www.dr-bob.org/cgi-bin/pb/mget.pl?post=/babble/20080105/msgs/805921.html#805921
I know that i suppose to take 50-100mgs of sulpiride, but it starts to feel like an anti-psychotice at this dosage.This worked well for the first 3 weeks, but know, i feel that i have developed a big tolerence towards to Selegiline.. I don't feel its activating, mood-lifting effect any longer... :( I haven't tried more than 15mg daily.
Posted by undopaminergic on March 19, 2008, at 15:48:28
In reply to Re: Amisulpride - and Sulpiride - Selegiline too » undopaminergic, posted by Amigan on March 19, 2008, at 14:16:04
> > I've tried both SULP and AMI, but it's only with the former that I've had the opportunity to experience the "dopamine rush" - a stimulant effect that beats methylphenidate (including high doses) by a wide margin in my experience.
>
>
> That's exactly what i needed to know. No "dopamine rush" with Sulp, while you experienced a notable effect with Ami. Interesting!! Maybe Amisulpride worths its money afterall.You misread me. I tried SULP first, and because I had no tolerance at that point, I experienced the dopamine rush. Later, I acquired AMI mostly for comparison, while I was still taking SULP. Switching from one agent to the other resulted in no remarkable effects, except that I have the faint impression that AMI may be slightly more potent. It will be interesting to see if the DA rush can be reproduced with AMI after some time of abstinence.
The price difference may depend on where you buy the medicines, but if you consider that you need fewer doses of AMI, you may find the difference more modest.
> http://www.dr-bob.org/cgi-bin/pb/mget.pl?post=/babble/20080105/msgs/805921.html#805921
> I know that i suppose to take 50-100mgs of sulpiride, but it starts to feel like an anti-psychotice at this dosage.
>
> This worked well for the first 3 weeks, but know, i feel that i have developed a big tolerence towards to Selegiline.. I don't feel its activating, mood-lifting effect any longer... :( I haven't tried more than 15mg daily.I usually notice the stimulating effects of selegiline for 1-2 days at most, and only after a long time of abstinence. However, selegiline has subtle benefits such as the potentiation of other drugs, and 15% increased life-span or so like the rats Knoll wrote about in one of his articles.
If you want more noticeable effects of selegiline as monotherapy, you need to increase the dose further until the combined effects of MAO-inhibition and amphetamine metabolites become unmistakeable. This style of selegiline-usage has not been well publicised, but would be interesting to learn about.
Posted by Amigan on March 19, 2008, at 16:33:21
In reply to Re: Amisulpride - and Sulpiride - Selegiline too, posted by undopaminergic on March 19, 2008, at 15:48:28
> > > I've tried both SULP and AMI, but it's only with the former that I've had the opportunity to experience the "dopamine rush" - a stimulant effect that beats methylphenidate (including high doses) by a wide margin in my experience.
> >
> >
> > That's exactly what i needed to know. No "dopamine rush" with Sulp, while you experienced a notable effect with Ami. Interesting!! Maybe Amisulpride worths its money afterall.
>
> You misread me.Oh, sorry. You are right. For some reason, i thought that the "former" was Amisulpride. Sulpiride is ok then..
> I tried SULP first, and because I had no tolerance at that point, I experienced the dopamine rush. Later, I acquired AMI mostly for comparison, while I was still taking SULP. Switching from one agent to the other resulted in no remarkable effects, except that I have the faint impression that AMI may be slightly more potent. It will be interesting to see if the DA rush can be reproduced with AMI after some time of abstinence.
Yes, it will be intersting to see that. Keep us informed, please.
> The price difference may depend on where you buy the medicines, but if you consider that you need fewer doses of AMI, you may find the difference more modest.
>
> > http://www.dr-bob.org/cgi-bin/pb/mget.pl?post=/babble/20080105/msgs/805921.html#805921
> > I know that i suppose to take 50-100mgs of sulpiride, but it starts to feel like an anti-psychotice at this dosage.
> >
> > This worked well for the first 3 weeks, but know, i feel that i have developed a big tolerence towards to Selegiline.. I don't feel its activating, mood-lifting effect any longer... :( I haven't tried more than 15mg daily.
>
> I usually notice the stimulating effects of selegiline for 1-2 days at most, and only after a long time of abstinence. However, selegiline has subtle benefits such as the potentiation of other drugs, and 15% increased life-span or so like the rats Knoll wrote about in one of his articles.
>
> If you want more noticeable effects of selegiline as monotherapy, you need to increase the dose further until the combined effects of MAO-inhibition and amphetamine metabolites become unmistakeable. This style of selegiline-usage has not been well publicised, but would be interesting to learn about.I plan to push the dose at 25mg once or twice just to see how i will react. I don't thing that i will retain this dosage because i will be running out of selegiline in no time, plus that i will have to follow the MAOI diet.
I wonder in what degree the metabolites will contribute to an activating effect, since they are levo- stereoisomers and hence they are expected to have peripheral effect mainly.
Posted by RMarie on March 19, 2008, at 23:02:17
In reply to Re: Amisulpride - and Sulpiride - Selegiline too » undopaminergic, posted by Amigan on March 19, 2008, at 14:16:04
Just wondering what your major problem/ problems are? Are you bi-polar or depression, anxiety only? Curious as I was thinking of augmenting Selegeline with Sulpride but isn't it (Sulpride) used for schizophrenia, etc. I have depression & anxiety so not sure Any suggestions? Thanks.
Posted by Amigan on March 19, 2008, at 23:51:36
In reply to Re: Amisulpride - and Sulpiride - Selegiline too, posted by RMarie on March 19, 2008, at 23:02:17
I use this combination for ADHD, dysthymia and chronic fatigue. It might be good for your depression if it's the atypical kind, but not good for your anxiety.
Posted by Basia on March 20, 2008, at 6:39:02
In reply to Re: Amisulpride - and Sulpiride - Selegiline too, posted by Amigan on March 19, 2008, at 23:51:36
I was on Sulpiride for ten years and also tried Amisulpiride for a month or two as they thought an atypical would be less dangerous and freer of side effects.Amisulpiride did not work.
Apart from schizoaffective disorder, I also have a diagnosis of HPPD. I have noticed that atypicals can worsen this and have been on Clozapine, Olanzapine , Loxapine, Haloperidol, Stelazine and others with limited success. Sulpiride has been the only one that has got rid of my HPPD and psychosis completely. However, it is too dangerous for me to stay on it as my prolactin was sky high and I stopped menstruating and developed thinning bones at the tender age of 30 - I am now 34. I did notice that the anti-depressant action of Sulpiride stopped after a year but I went up to 800mg, which enabled me to work and socialise very effectively for all those years. I was then put on Lamotrigine for suicidal depression and this saved my life.I am now on Seroquel and dealing with harsh side effects and a return of HPPD. I am wondering whether atypicals' effect on a wider range of receptors may be to blame. I have heard that Risperidone can worsen HPPD.
Any ideas?
Thanks!
Lyn
Posted by undopaminergic on March 20, 2008, at 19:02:40
In reply to Re: Amisulpride - and Sulpiride - Selegiline too, posted by Amigan on March 19, 2008, at 23:51:36
> I use this combination for ADHD, dysthymia and chronic fatigue. It might be good for your depression if it's the atypical kind, but not good for your anxiety.
>It may be slightly effective against anxiety too, but first and foremost, in my experience, it improves motivation, initiative, (mental) energy and executive function. For me, it was clearly no euphoriant even at its best.
Posted by undopaminergic on March 20, 2008, at 20:09:14
In reply to Question re Amisulpride - and Sulpiride, posted by Basia on March 20, 2008, at 6:39:02
> I was on Sulpiride for ten years and also tried Amisulpiride for a month or two as they thought an atypical would be less dangerous and freer of side effects.Amisulpiride did not work.
> Apart from schizoaffective disorder, I also have a diagnosis of HPPD. I have noticed that atypicals can worsen this and have been on Clozapine, Olanzapine , Loxapine, Haloperidol, Stelazine and others with limited success. Sulpiride has been the only one that has got rid of my HPPD and psychosis completely. However, it is too dangerous for me to stay on it as my prolactin was sky high and I stopped menstruating and developed thinning bones at the tender age of 30 - I am now 34. I did notice that the anti-depressant action of Sulpiride stopped after a year but I went up to 800mg, which enabled me to work and socialise very effectively for all those years. I was then put on Lamotrigine for suicidal depression and this saved my life.
>
> I am now on Seroquel and dealing with harsh side effects and a return of HPPD. I am wondering whether atypicals' effect on a wider range of receptors may be to blame. I have heard that Risperidone can worsen HPPD.
>
> Any ideas?It makes sense, because sulpiride and amisulpride (and possibly some other benzamides) affect the narrowest range of receptors - or in other words, are the most selective - of the dopamine antagonists used clinically. They also cross the blood-brain-barrier (BBB) with difficulty relative to most other antipsychotics (except perhaps risperidone), which means that at doses that produce the desired degree of dopamine-antagonism in the CNS, they produce a more effective peripheral DA-blockade in comparison with agents that cross the BBB more freely. One of the consequences is the blockade of DA-receptors in the pituitary, resulting in disinhibition of prolactin secretion. Through a chain of events, the prolactin produces diminished gonadal activity (hypogonadism) and thus a deficit of sex hormones. In theory, it should be possible to correct the deficiency with hormone supplements, and there are other options as well for preventing and/or reversing bone loss.
Posted by undopaminergic on March 23, 2008, at 3:26:22
In reply to Re: Amisulpride - and Sulpiride - Selegiline too » undopaminergic, posted by Amigan on March 19, 2008, at 16:33:21
>
> > I tried SULP first, and because I had no tolerance at that point, I experienced the dopamine rush. Later, I acquired AMI mostly for comparison, while I was still taking SULP. Switching from one agent to the other resulted in no remarkable effects, except that I have the faint impression that AMI may be slightly more potent. It will be interesting to see if the DA rush can be reproduced with AMI after some time of abstinence.
>
> Yes, it will be intersting to see that. Keep us informed, please.Unfortunately, upon restarting amisulpride (AMI, 50 mg), there was little or no effect, despite more than a week of not taking anything with the same mechanism of action. During the time off from AMI, I also took selegiline (5-10 mg), which in the past has helped reverse tolerance to sulpiride (SULP). Therefore, I propose that methylphenidate and/or modafinil induce cross-tolerance to AMI/SULP. This doesn't particularly surpise me - in fact, at this point I was expecting it. Probably, the mechanism of tolerance is downregulation of post-synaptic dopamine (DA) receptors, which would account for the lack of significance of whether the elevated synaptic DA concentrations were a result of DA transporter blockade (methylphenidate, modafinil) or autoreceptor blockade (AMI, SULP). Alternatively, there is some other neurotransmitter system that becomes upregulated by chronic DA agonism, and has antagonistic effects upon one or more aspects of dopaminergic transmission.
Posted by Amigan on March 23, 2008, at 13:05:45
In reply to Re: Amisulpride - and Sulpiride - Selegiline too, posted by undopaminergic on March 23, 2008, at 3:26:22
Posted by kingcolon on March 31, 2008, at 23:37:40
In reply to Re: Amisulpride - and Sulpiride - Selegiline too, posted by undopaminergic on March 23, 2008, at 3:26:22
I propose that methylphenidate and/or modafinil induce cross-tolerance to AMI/SULP. This doesn't particularly surpise me - in fact, at this point I was expecting it. Probably, the mechanism of tolerance is downregulation of post-synaptic dopamine (DA) receptors, which would account for the lack of significance of whether the elevated synaptic DA concentrations were a result of DA transporter blockade (methylphenidate, modafinil) or autoreceptor blockade (AMI, SULP). Alternatively, there is some other neurotransmitter system that becomes upregulated by chronic DA agonism, and has antagonistic effects upon one or more aspects of dopaminergic transmission.
Do you have a reference to dopaminergic activity of modafinil? I have not seen any literature that suggests it has significant dopaminergic action--it is frequently mentioned that it is nonaddictive because it lacks activity in the mesolimbic system.
Posted by undopaminergic on April 2, 2008, at 1:32:07
In reply to Re: Amisulpride - and Sulpiride - Selegiline too, posted by kingcolon on March 31, 2008, at 23:37:40
>
> Do you have a reference to dopaminergic activity of modafinil? I have not seen any literature that suggests it has significant dopaminergic action--it is frequently mentioned that it is nonaddictive because it lacks activity in the mesolimbic system.
>Addictiveness is relative, determined by numerous factors. I have no doubt that modafinil can be addictive to certain people under certain circumstances.
The most important feature of modafinil identified so far appears to be its blockade of the dopamine transporter, although it has other properties too.
"Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro."
http://www.ncbi.nlm.nih.gov/pubmed/16885432"Dopaminergic role in stimulant-induced wakefulness."
http://www.ncbi.nlm.nih.gov/pubmed/11222668
Posted by kingcolon on April 2, 2008, at 14:07:24
In reply to Re: Amisulpride - and Sulpiride - Selegiline too, posted by undopaminergic on April 2, 2008, at 1:32:07
>
> >
> > Do you have a reference to dopaminergic activity of modafinil? I have not seen any literature that suggests it has significant dopaminergic action--it is frequently mentioned that it is nonaddictive because it lacks activity in the mesolimbic system.
> >
>
> Addictiveness is relative, determined by numerous factors. I have no doubt that modafinil can be addictive to certain people under certain circumstances.
>
> The most important feature of modafinil identified so far appears to be its blockade of the dopamine transporter, although it has other properties too.
>
>
> "Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro."
> http://www.ncbi.nlm.nih.gov/pubmed/16885432
>
> "Dopaminergic role in stimulant-induced wakefulness."
> http://www.ncbi.nlm.nih.gov/pubmed/11222668
>
>Thanks! The 2006 study seems like a good one.
This is the end of the thread.
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