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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by DarbyZ. on September 20, 1999, at 19:25:15
I would like to try the new drug Pramipexole for my depression, just a small amount to see if it might work for me. Can it be ordered from overseas pharmacies? Does anyone out there have a small, unused supply they'd like to get rid of?
The same with Amisulpride (Solian), another D2/D3 drug. Any suggestions?
Posted by Bruce on September 21, 1999, at 7:34:01
In reply to Pramipexole (Mirapex) For Depression, posted by DarbyZ. on September 20, 1999, at 19:25:15
> I would like to try the new drug Pramipexole for my depression, just a small amount to see if it might work for me. Can it be ordered from overseas pharmacies? Does anyone out there have a small, unused supply they'd like to get rid of?
> The same with Amisulpride (Solian), another D2/D3 drug. Any suggestions?
I have been aggresively checking for Mirapex from an overseas pharmacy. No one seems to offer it (without a prescription). If they do, they aren't advertising it.Bruce
Posted by verac on June 23, 2000, at 12:26:00
In reply to Re: Pramipexole (Mirapex) For Depression, posted by Bruce on September 21, 1999, at 7:34:01
> > I would like to try the new drug Pramipexole for my depression, just a small amount to see if it might work for me. Can it be ordered from overseas pharmacies? Does anyone out there have a small, unused supply they'd like to get rid of?
> > The same with Amisulpride (Solian), another D2/D3 drug. Any suggestions?
>
>
> I have been aggresively checking for Mirapex from an overseas pharmacy. No one seems to offer it (without a prescription). If they do, they aren't advertising it.
>
> Bruce
For your reference, Pramipexole is available just north of you here in Canada -called Mirapex. The data available however is only Parkinsons related with no reference whatsoever to depression. Has anyone any data at all on its use for major unipolar depression?
Thanks very much, verac
Posted by Jonathan on June 23, 2000, at 22:38:19
In reply to Re: Pramipexole (Mirapex) For Depression, posted by verac on June 23, 2000, at 12:26:00
> > > I would like to try the new drug Pramipexole for my depression, just a small amount to see if it might work for me. Can it be ordered from overseas pharmacies? Does anyone out there have a small, unused supply they'd like to get rid of?
> > > The same with Amisulpride (Solian), another D2/D3 drug. Any suggestions?
> >
> > I have been aggresively checking for Mirapex from an overseas pharmacy. No one seems to offer it (without a prescription). If they do, they aren't advertising it.
> > Bruce
>
> For your reference, Pramipexole is available just north of you here in Canada -called Mirapex. The data available however is only Parkinsons related with no reference whatsoever to depression. Has anyone any data at all on its use for major unipolar depression?
> Thanks very much, veracWow, this is _very_ interesting. I hope you get to try it, Bruce. Please let us know how you get on.
Below is the abstract of a recent paper which includes dosage details and a comparison with Prozac for major unipolar depression.
As a general rule with many exceptions, drugs for which the clinically effective daily dose is 100 mg/day are often best avoided unless there's no 'cleaner' alternative. Pramipexole, it seems, is no exception to this rule.
Another 'rule' of arguably dubious validity, which pramipexole could change, is: don't mess with dopamine (DA) until all other alternatives have failed, because DA has so many different actions and receptor subtypes. On the other hand, antidepressants which act on DA systems indirectly, via serotonergic and/or noradrenergic systems, are so slow.
What's interesting about pramipexole (and not clear from this abstract) is that at low doses it's an agonist at D2, D3 and (probably) D4 receptors, with the highest affinity for D3; this D3 selectivity is what makes it different from other DA receptor agonists that I've heard of.
If I remember correctly, some D2 receptors (but not all) are presynaptic and modulate synaptic dopamine levels, thus affecting all postsynaptic receptor types: the antidepressant amisulpride, a D2 antagonist (the opposite of pramipexole!) stimulates all postsynaptic DA receptors, including D3, indirectly by raising DA levels: pramipexole, however, lowers DA levels but stimulates D3 receptors directly and therefore more selectively.
I'd be grateful if anyone can add to and/or correct this; in particular, which DA receptor types are likely to be involved in which types of depression?
Jonathan.
Here's the abstract:
TI: Comparison of pramipexole, fluoxetine, and placebo in patients
with major depression
AU: Corrigan_MH, Denahan_AQ, Wright_CE, Ragual_RJ, Evens_DL
NA: PHARMACIA & UPJOHN INC,GLOBAL CLIN RES,MS 7278-NJ-260,95 CORP
DR,POB 6995,BRIDGEWATER,NJ,08807
PHARMACIA & UPJOHN INC,CNS DEV,KALAMAZOO,MI,49001
PHARMACIA & UPJOHN INC,CLIN BIOSTAT 2,KALAMAZOO,MI,49001
UNIV PENN HLTH SYST,DEPT PSYCHIAT,PHILADELPHIA,PA
JN: DEPRESSION AND ANXIETY, 2000, Vol.11, No.2, pp.58-65
IS: 1091-4269
DT: Article
AB: Pramipexole, a dopamine D-2 receptor agonist, was tested in 174
patients with major depression, with or without melancholia and
without psychotic features. Three daily dose bevels (0.375 mg,
1.0 mg, and 5.0 mg) were compared to fluoxetine (Prozac) at 20
mg and placebo in a randomized, double-blind, parallel-group
study. After a 1 week placebo ran-in period patients were
treated for 8 weeks, had a post-study follow-up (week 9), and
were evaluated primarily with the Hamilton Psychiatric Rating
Scale for Depression (HAM-D), the Montgomery-Asberg Depression
Rating Scale (MADRS), and the Clinician's Global Impressions-
Severity of Illness scale (CGI-SI), All patients who received
one nose of study medication were included in the observed-case
analysis (no missing data were replaced), Results indicated
that by endpoint (week 8), patients receiving pramipexole at
the 1.0 mg per day dose had significant improvement over
baseline compared to the placebo group by measure of the HAM-D,
MADRS, and CGI-SI, Significant improvement in this nose group
was seen at other timepoints as well. The most obvious
improvement was seen in the pramipexole 5.0 mg group, although
a substantial dropout rate for this group precluded statistical
tests vs, placebo late in the study. Patients taking fluoxetine
also showed significant improvements at endpoints on the MADRS
and earlier in the study on the HAM-D, No new or unusual safety
concerns were generated during this study. Pramipexole helped
safely alleviate the symptoms of depression at 1.0 mg per day
and especially in those patients who could tolerate the
escalation to 5 mg per day, (C) 2000 Wiley-Liss, Inc.
Posted by Jonathan on June 24, 2000, at 7:45:55
In reply to Re: Pramipexole (Mirapex) For Depression » verac, posted by Jonathan on June 24, 2000, at 1:27:23
The third sentence of my post "Re: Pramipexole (Mirapex) for Depression, to verac" was meant to read
"As a general rule with many exceptions, drugs for which the clinically effective daily dose is less than 10 mg are clean and specific, with relatively few bad side effects, whilst those dosed at more than 100 mg/day are often best avoided unless there's no 'cleaner' alternative. Pramipexole, it seems, is no exception to this rule."
According to the Dr Bob's FAQ at http://www.dr-bob.org/babble/faq.html#links:
"Can I put HTML tags in my messages?
No, you cannot put HTML tags in your messages. At least not now. I'll try to be open to feedback, but I'm afraid HTML tags would lead to trouble."
I've just discovered that even unintended HTML tags can lead to trouble. In the offending sentence, between the words
"...dose is" and "100 mg/day..." I wrote:
".LT. 10 mg are clean and specific, with relatively few bad side effects, whilst those dosed at .GT."
where .LT. is the 'less than' sign (shift-, on most keyboards), while .GT. means 'greater than' (shift-.).LT., .GT. and all the words in between seem to have been treated as an HTML tag and filtered out. The filtered version still looks like coherent English, but it's pharmacological gibberish and not what I said.
Jonathan.
Posted by AndrewB on June 24, 2000, at 9:41:12
In reply to Re: Pramipexole (Mirapex) For Depression » verac, posted by Jonathan on June 24, 2000, at 1:27:23
I've taken both pramipexole (Mirapex) and amisulpride. I have a combo of dysthymia, social anxiety, and some variant of Chronic Fatigue. The amisulpride was effective in removing the greater proportion of my dysthymia, my social anxiety and my chronic fatigue. Amisulpride kicks in and starts working for me in only 4 days. For more information on amisulpride and how to obtain it, email me at andrewb@seanet.com for an information piece.
Pramipexole was not effective for me however. Which is curious since pramipexole is very similar in action to amisulpride. Both act specifically on the D2-D3 receptors. The amisulpride antagonizes the presynaptic receptors while Mirapex is a postsynaptic agonist. Possibly, others are like me. They respond very well to one of these meds but not the other.
Pramipexole is only available, I believe, in the US and Canada with a prescription. Requip though is available in Britain and many other countries and appears to have an D3/D3 agonist action much like pramipexole and it has been suggested that it may have a similar antidepressant potential to pramipexole.
AndrewB
Posted by SLS on June 24, 2000, at 15:02:51
In reply to Re: Pramipexole (Mirapex) For Depression, posted by AndrewB on June 24, 2000, at 9:41:12
> I've taken both pramipexole (Mirapex) and amisulpride. I have a combo of dysthymia, social anxiety, and some variant of Chronic Fatigue. The amisulpride was effective in removing the greater proportion of my dysthymia, my social anxiety and my chronic fatigue. Amisulpride kicks in and starts working for me in only 4 days. For more information on amisulpride and how to obtain it, email me at andrewb@seanet.com for an information piece.
>
> Pramipexole was not effective for me however. Which is curious since pramipexole is very similar in action to amisulpride. Both act specifically on the D2-D3 receptors. The amisulpride antagonizes the presynaptic receptors while Mirapex is a postsynaptic agonist. Possibly, others are like me. They respond very well to one of these meds but not the other.
>
> Pramipexole is only available, I believe, in the US and Canada with a prescription. Requip though is available in Britain and many other countries and appears to have an D3/D3 agonist action much like pramipexole and it has been suggested that it may have a similar antidepressant potential to pramipexole.
>
> AndrewB
Dear Andrew,Mirapex and amisulpride are more like opposites at the level of receptor function. I don't think it serves well to consider them as being similar in action. Mirapex stimulates while amisulpride inhibits DA receptors. The reason amisulpride may exert an antidepressant effect at low dosages is that it prefers to bind to presynaptic DA autoreceptors as compared to postsynaptic receptors.
I want to learn more about the relative affinities of Mirapex for different DA receptors, particularly D3.
A few questions for Andrew:1. Does Mirapex antagonize the antidepressant effects of amisulpride or sulpiride. Have you ever taken amisulpride and Mirapex in combination?
2. How does Mirapex compare to the other DA agonist Parkinson's drugs for treating depression?
3. What information have you run across regarding efficacy of Requip in treating depression?
4. Do DA D3 receptors appear as presynaptic autoreceptors?
3. At what dosage of amisulpride did you first begin to respond? What dosage did you end up with?
Thanks.
- Scott
Posted by AndrewB on June 25, 2000, at 12:32:25
In reply to Re: Pramipexole (Mirapex) For Depression » AndrewB, posted by SLS on June 24, 2000, at 15:02:51
> Dear Andrew,
>
> Mirapex and amisulpride are more like opposites at the level of receptor function. I don't think it serves well to consider them as being similar in action. Mirapex stimulates while amisulpride inhibits DA receptors. The reason amisulpride may exert an antidepressant effect at low dosages is that it prefers to bind to presynaptic DA autoreceptors as compared to postsynaptic receptors.
>
You and I have gone over this before. Both amisulpride's and Mirapex's antidepressant effects are thought to be due to their ability to increase firing of the D2/D3 (postsynaptic) receptors though they accomplish this by different actions. Call them opposties if you wish.> I want to learn more about the relative affinities of Mirapex for different DA receptors, particularly D3.
Mirapex has a ten times greater affinity for D3 receptors than D2 and a preference for receptors in the striatum over the limbic system.
>
> A few questions for Andrew:
>
> 1. Does Mirapex antagonize the antidepressant effects of amisulpride or sulpiride. Have you ever taken amisulpride and Mirapex in combination?
>
I had taken Mirapex and amisulpirde together for over 2 months. They do not antagonize each other or, in my experience, enhance one another. The only changes I noticed with the addition of Mirapex was a lot of crying during tear jerker movies and a greatly improved jump shot!> 2. How does Mirapex compare to the other DA agonist Parkinson's drugs for treating depression?
>
No comparison studies have been made.> 3. What information have you run across regarding efficacy of Requip in treating depression?
>
None, I’ve only read of speculation that Requip would have similar antidepressant action to Mirapex. Requip has a 10 fold selectivity for the D3 recpetor over the D2 recpetor. It is a D2/D3/D4 agonist.> 4. Do DA D3 receptors appear as presynaptic autoreceptors?
Yes. I researched this since it was my impression that every D2 and D3 postsynaptic receptor was matched (across the synapse) with an (presynaptic) autoreceptor. This may or may not be true. D3 autoreceptors do exist however.
>
> 3. At what dosage of amisulpride did you first begin to respond? What dosage did you end up with?I started with 50mg./day and I am currently at 50mg/day. 100mg has slightly less effect for me.
>
Scott, I will be gone for a week.AndrewB
This is the end of the thread.
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