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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by Bruce on December 15, 1999, at 8:31:10
I was trolling through Usenet and came across a supplier.
Apparently it's a UK company.
A Usenet reader posted some prices on Requip (a dopamine agonist), pindolol, and others. Mirapex (another D2/D3 agonist) is also apparently available.
Caveat: I have no experience whatsoever with these people. They could be crooks for all I know. Their website does say that no prescription is necessary. A price quote for your specific medicine(s) is delivered via email.
Bruce
Posted by andrewb on December 15, 1999, at 10:21:41
In reply to New Offshore Supplier! Mirapex available!, posted by Bruce on December 15, 1999, at 8:31:10
I haven't used them myself but I have read that they have an excellent reputation for service.
Posted by andrewb on December 17, 1999, at 12:24:04
In reply to New Offshore Supplier! Mirapex available!, posted by Bruce on December 15, 1999, at 8:31:10
I just got a response back. They say they don't have Mirapex. There is no UK equivelent. But if they do indeed have Requip (ropinirole), it may have similar a antidepressant action as Mirapex. Both are striatum D2 receptor agonists (non ergot).
Posted by Bruce on December 20, 1999, at 7:51:31
In reply to Re: New Offshore Supplier! Mirapex available!, posted by andrewb on December 17, 1999, at 12:24:04
> I just got a response back. They say they don't have Mirapex. There is no UK equivelent. But if they do indeed have Requip (ropinirole), it may have similar a antidepressant action as Mirapex. Both are striatum D2 receptor agonists (non ergot).
Well done, AndrewB! I guess I should be more thorough and ask first before posting what I read on Usenet...At any rate, Requip is available, and has a similar action to Mirapex. Interestingly, both drugs now have a warning of somnolence (which apparently happens to a large percentage of users) - that is odd considering they are dopamine agonists. You'd think they'd be energizing. I may yet try amisulpride.
Bruce
Posted by Scott L. Schofield on December 28, 1999, at 9:50:21
In reply to Re: New Offshore Supplier! Mirapex available!, posted by Bruce on December 20, 1999, at 7:51:31
> At any rate, Requip is available, and has a similar action to Mirapex.What are the generic names for Requip and Mirapex?
> Interestingly, both drugs now have a warning of somnolence (which apparently happens to a large percentage of users) - that is odd considering they are dopamine agonists. You'd think they'd be energizing. I may yet try amisulpride.
This effect is seen quite often when low doses of some direct dopamine agonists are used. Presynaptic dopamine autoreceptors tend to be “stronger” than the postsynaptic receptors at attracting the neurotransmitter. These autoreceptors, when stimulated by the attachment of a natural neurotransmitter molecule or a drug that mimics it, tells the presynaptic neuron to “power-down” by decreasing the amount of dopamine being manufactured as well as releasing smaller amounts of it. At low dosages, a greater ratio of the stronger presynaptic autoreceptors are stimiulated as compared with those that are postsynaptic. The consequence of this is a reduction in the number of postsynaptic dopamine neurons firing and a resultant state of sedation. At higher dosages, basically all of the receptors are stimulated, including the postsynaptic ones that cause the stimulation otherwise associated with these drugs.
Amisulpiride works exactly in reverse. It is a dopamine receptor antagonist. It sticks to the receptors without stimulating them. It therefore blocks the receptor from capturing the dopamine that would otherwise stimulate it. At low dosages, more presynaptic autoreceptors are blocked than are postsynaptic, so the first neuron is convinced that it needs to manufacture and release more dopamine while there are still enough open receptors on the second neuron to be stimulated by it. This is what may account for its antidepressant effects. At higher dosages, the receptors of the postsynaptic neuron are blocked, leading to its inhibition. This is what is thought to be responsible for its anti-psychotic properties and why it has been used for schizophrenia.
- Scott
Posted by andrewb on December 29, 1999, at 12:01:19
In reply to Re: New Offshore Supplier! Mirapex available!, posted by Scott L. Schofield on December 28, 1999, at 9:50:21
Scott,
Thank you for your very interesting posting. To answer your question, the generic name for Mirapex is pramipexole and the generic for Requip is ropinirole. Both are non-ergot D2 receptor agonists that act on the striatum.
I have recently had what seems like a partial poop out on amisulpride after 4 months of effectiveness. That is less energy, more daytime sleepiness and less motivation. Another person wrote that she experienced poop out after an initial robust response to Mirapex. It occurs to me that maybe we aren't experiencing poop out after all, rather I may be taking too much amisulpride and she too little Mirapex. I am taking 100 mgs/day of amisulpride though studies have shown 50 mgs./day to be just as effective. Any ideas here. What would happen if a dopamine agonist like Mirapex was combined with Amisulpride. Could this possibly be an more effective antidepressant cocktail. I also was wondering what the difference was between ropinirole and pramipexole. Perhaps the only difference is the relative degree of binding affinity to the D2 (and D3?) receptors but to the patient pretty much the same effect is experienced.
Thanks for any info.,Andrew
Posted by Scott L. Schofield on December 30, 1999, at 7:42:25
In reply to Re: to Scott, posted by andrewb on December 29, 1999, at 12:01:19
> I have recently had what seems like a partial poop out on amisulpride after 4 months of effectiveness. That is less energy, more daytime sleepiness and less motivation. Another person wrote that she experienced poop out after an initial robust response to Mirapex. It occurs to me that maybe we aren't experiencing poop out after all, rather I may be taking too much amisulpride and she too little Mirapex. I am taking 100 mgs/day of amisulpride though studies have shown 50 mgs./day to be just as effective. Any ideas here. What would happen if a dopamine agonist like Mirapex was combined with Amisulpride. Could this possibly be an more effective antidepressant cocktail. I also was wondering what the difference was between ropinirole and pramipexole. Perhaps the only difference is the relative degree of binding affinity to the D2 (and D3?) receptors but to the patient pretty much the same effect is experienced.
I wish I hadn’t been forced to drop out of college as a sophomore because of this damned thing. I would have had a better perspective and greater confidence in what I *think* I know. I do know that some drugs display a “therapeutic window”. A therapeutic window represents the range of dosages (or blood-levels, etc.) within which a drug will be effective. The word “window” is used to convey the idea that there is a minimum dosage and a maximum dosage within which the drug will exert its therapeutic effect. This therapeutic effect is lost if the dosage is too low or too high.
As far as amisulpiride is concerned, I think that there may be a better chance of it having a stable therapeutic window as compared to pramipexole. Your guess may be right and you could be taking too much. Low dosages of other neuroleptics have been used with varying degrees of success as antidepressants. One of the more promising drugs for this usage is olanzapine (Zyprexa).
The augmentation of antidepressants using direct-acting (ligand) dopamine agonists such as bromocryptine and pergolide has been used in the past. I have read some pretty persuasive anecdotes that support this practice. I’m not so convinced that it is so effective long-term. The few people I know who have tried it (myself included) have experienced and initial improvement followed by a plateauing and then relapse. Perhaps there are properties possessed by pramipexole that foster a continued response. For now, I just don’t have that much confidence in using DA agonists. Perhaps it is the development of postsynaptic receptor subsensitivity that might require the need for higher and higher dosages until some upper-bound is reached. This would especially be likely if the presynaptic neuron were inhibited by the stimulation of its autoreceptors. I can’t remember what all of the different dopamine receptors do or where they are located, but it seems reasonable that a compound that is a specific (rather than selective) agonist of postsynaptic receptors may be less liable to end in burn-out.
I have never thought of combining a DA agonist with a DA antagonist. It is an intriguing proposition. What if one were to combine a selective presynaptic antagonist with a selective postsynaptic agonist? Interesting stuff.
Good thinking.
Sincerely,
Scott
This is the end of the thread.
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