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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 21 of 21. This is the beginning of the thread.
Posted by fires on October 19, 2005, at 15:25:23
Interesting:
Posted by CK1 on October 19, 2005, at 17:03:52
In reply to Triple reuptake inhibitor trial, posted by fires on October 19, 2005, at 15:25:23
Aren't these just new MAOI's?
Posted by Schess81 on October 19, 2005, at 18:37:28
In reply to Re: Triple reuptake inhibitor trial, posted by CK1 on October 19, 2005, at 17:03:52
You'd think the Triple reuptake inhibitors' clinical effect must be quite simaliar to the MAOIs- although they are slightly different, as MAO is an enzyme that breaks down excess nuerotransmiter in the synapse, and the triple reuptake inhibitors would prevent neurotransmitter reuptake back into the presynaptic neuron. Either way, both are going to increase the amount serotonin, norepiniphrine and dopamine in the synaptic gap. And of course the TRIs wouldnt have the dietary restrictions of the MAOIs.
Posted by Phillipa on October 19, 2005, at 19:33:02
In reply to Triple reuptake inhibitor trial, posted by fires on October 19, 2005, at 15:25:23
So does this mean that the drug companies are realizing that the current meds just don't work? Fondly, Phillipa
Posted by CK1 on October 19, 2005, at 19:56:53
In reply to Re: Triple reuptake inhibitor trial, posted by Phillipa on October 19, 2005, at 19:33:02
Okay so different modes of action but basically the same result as MAOI's, which have been around for decades. MAOI's without food restrictions :) Cool!
Posted by med_empowered on October 19, 2005, at 20:40:13
In reply to Re: Triple reuptake inhibitor trial, posted by CK1 on October 19, 2005, at 19:56:53
but..im a little concerned. I mean, with the SSRIs (and to some extent, the stimulants) there's a problem with reduced "firing" in the affected regions. If you you're reducing reuptake all over the place, it seems like you'd have the potential for some **horrible** withdrawal, and possibly a greater degree of "poop out" than with what we have now. It seems like the withdrawal could be as bad as high-dose Effexor..or worse.
Posted by Tom Twilight on October 20, 2005, at 12:44:59
In reply to Re: Triple reuptake inhibitor trial, posted by med_empowered on October 19, 2005, at 20:40:13
I don't mean to contradict anyone, and I'm just speculating, but I don't think triple re-uptake inhibitors will be the same as MAOIs.
For one thing their mechanism of action is very different, so that probably equalls different results.
Secondly the MAOI drugs we have do not act soley through MAOI inhibition.
Nardil, Parnate and Moclobemide are all MAOIs, but there all totaly different drugs.Nardil is skewed towards Serotonin and prevents the breakdown of GABA, Parnate is skewed towards Dopamine and enhances dopamine release (I think).
Posted by ed_uk on October 20, 2005, at 14:43:01
In reply to Triple reuptake inhibitors and MAOIs, posted by Tom Twilight on October 20, 2005, at 12:44:59
I agree with Tom. Triple reuptake inhibitors will not be similar to MAOIs.
~Ed
Posted by Iansf on October 20, 2005, at 18:34:27
In reply to Re: Triple reuptake inhibitors and MAOIs, posted by ed_uk on October 20, 2005, at 14:43:01
> I agree with Tom. Triple reuptake inhibitors will not be similar to MAOIs.
>
> ~EdBut will be the difference between them and, say, combining an SSRI with bupropion? Especially since for so many people, the real issue is side effects. A new med with the same side effects as existing ones isn't that much of an advance if it only does what a med cocktail can do already. I'd rather see drug companies focus on finding an effective med that does no more than existing meds do but has fewer and less potent side effects. I think it would help a far greater number of people, myself included.
Posted by SLS on October 20, 2005, at 19:24:56
In reply to Re: Triple reuptake inhibitors and MAOIs, posted by Iansf on October 20, 2005, at 18:34:27
Hi Iansf.
> > I agree with Tom. Triple reuptake inhibitors will not be similar to MAOIs.
> But will be the difference between them and, say, combining an SSRI with bupropion? Especially since for so many people, the real issue is side effects. A new med with the same side effects as existing ones isn't that much of an advance if it only does what a med cocktail can do already.
First of all, I doubt we can consider Wellbutrin to be a true DA reuptake inhibitor the way nomifensine and amineptine were. It is weak at best. Second of all, different is different. Some people respond to one SSRI and not another. Adding more complete and balanced monoamine uptake inhibitors can only improve an individual's chances of attaining remission. I usually welcome any addition to our arsenal, even if other people regard them as "me too" drugs. The adding or subtracting of a single atom can make all the difference in the world when it comes to therapeutic effect.
Regarding side effects, I believe that drug companies are indeed trying to "clean up" their drugs by doing things like separating out enantiomers and rejecting the one that is not responsible for the therapeutic effect in an effort to reduce side effects. One such example is Forest Labs and their Celexa -> Lexapro. Eli Lilly tried the same thing with Prozac, but ran into problems with dosing. Cephalon is in the process of doing the same thing with Provigil -> Nuvigil. People debate as to whether these efforts have offered true benefits.
There are several truly novel drugs in the research and development pipeline that attack depression from completely different angles. You might find some hope in looking at the following webpage:
www.neurotransmitter.net/newdrugs.html
Agomelatine is a novel antidepressant drug that should become available very soon in Europe. I believe the drug company will shortly thereafter begin work on getting it approved in the US. Agomelatine is a 5-HT2b/c antagonist and a melatonin M1/M2 agonist.
Believe me when I tell you, I feel the same as most other people here that the pace of drug discovery is too slow. Development seems to come in waves of drugs that are similar to each other. That is just the nature of the drug companies to reflect the direction of knowledge and theory that emerges from neuroscience and psychopharmacology.
- Scott
Posted by Mistermindmasta on October 20, 2005, at 20:18:21
In reply to Triple reuptake inhibitor trial, posted by fires on October 19, 2005, at 15:25:23
> Interesting:
>
> http://finanzen.net/news/news_detail.asp?NewsNr=343315
>Dopamine reuptake inhibition would definitely mean abuse potential, I shall assume. I wonder how that will come into play.
Posted by SLS on October 20, 2005, at 21:47:09
In reply to Re: Triple reuptake inhibitor trial, posted by Mistermindmasta on October 20, 2005, at 20:18:21
Hi.
> Dopamine reuptake inhibition would definitely mean abuse potential, I shall assume. I wonder how that will come into play.
That might not necessarily be true. It might depend on which specific brain structures are affected. Nomifensine did not seem to have any abuse potential at all, and amineptine was at worst only of moderate risk. Still, I think you make a good point as to how the perception of abuse potential will affect a drug's approvability by regulatory agencies.
There are many important drugs that are used therapeutically by the ill that have the potential to be abused by the healthy. I don't find potential abusability to be a sufficient criterion to keep such drugs off the market. Cocaine still has valid uses as a topical anaesthetic for which a legal supply and distribution system exists.
- Scott
Posted by Chairman_MAO on October 21, 2005, at 0:18:18
In reply to Re: Triple reuptake inhibitors and MAOIs, posted by SLS on October 20, 2005, at 19:24:56
I feel that drug companies come out with single-entianomer drugs because it's cheaper than R&D, plain and simple. Why develop a totally new drug--even if it helps more people, is simply better, etc--when you can re-patent an entianomer?
Posted by med_empowered on October 21, 2005, at 5:43:17
In reply to Re: Triple reuptake inhibitors and MAOIs » SLS, posted by Chairman_MAO on October 21, 2005, at 0:18:18
It seems that, in treating depression, "abuse potential" is a big problem. Never mind that the Adderall and Ritalin we hand out like candy (at least in the US) can cause some serious problems and they're both schedule II substances; if an antidepressant has even a hint of abuse-potential, it gets black-balled. Look at amineptine. There were a few recorded cases of abuse, but they occured mostly in people with other problems--polydrug users, people with personality disorders, etc. And yet...amineptine has been pushed off the scene, leaving us with such fun drugs as Zoloft to take its place. It also seems like drug companies prefer to re-hash old drugs, make "new" combo drugs (ex: Symbyax), or make lots of "me-too" drugs instead of doing anything terribly innovative or helpful. And yet...we (especially in the US) are still expected to pay inflated drug prices for meds that are often pretty old, unoriginal, and only moderately effective, at best. Great system.
Posted by SLS on October 21, 2005, at 8:24:08
In reply to Re: Triple reuptake inhibitors and MAOIs » SLS, posted by Chairman_MAO on October 21, 2005, at 0:18:18
> I feel that drug companies come out with single-entianomer drugs because it's cheaper than R&D, plain and simple. Why develop a totally new drug--even if it helps more people, is simply better, etc--when you can re-patent an entianomer?
I know. However, there are people who report experiential differences between racemate and enantiomereric preparations of citalopram. However, I don't see any new enantiomeric antidepressants of previous racemates poised for development. It seems that the drug companies in general have not opted to go this route to produce patentable antidepressant drugs for market.
The wave of SSRIs seems to have crested with no new ones to be marketed. It would be sad if there were more SSRI compounds that don't produce as many side effects as those currently available that will forever remain on R&D shelves.
A new, small wave of multiple reuptake inhibitors is on the way. Beyond that are a collection of prototypic drugs of varying properties. The drug companies must feel that they have exhausted the market for amine uptake inhibitors. Instead of capitalism working to produce more effective and better uptake inhibitors, it is working to reduce them in an effort to find new marketing niches. The public has mistakenly deemed all uptake inhibitors as "me too" drugs. This is a shame. If we were stuck with only one each of MAOI, TCA, SSRI, and SNRI, the world would be a much more depressed place to live. "Me too" is really "Not exactly you". That difference is enough to get more people well. Once neuroscientists understand exactly what's going on will it be in a better position to establish exactly what "me too" is and is not.
- Scott
Posted by linkadge on October 21, 2005, at 10:38:00
In reply to Re: Triple reuptake inhibitors and MAOIs, posted by SLS on October 21, 2005, at 8:24:08
Yeah and tripple uptake inhibitor withdrawl?
Not only will you feel blue as hell, you'll also have zero energy and zero drive to boot.
Linkadge
Posted by ed_uk on October 21, 2005, at 14:16:55
In reply to Re: Triple reuptake inhibitors and MAOIs, posted by med_empowered on October 21, 2005, at 5:43:17
Hi Med!
>And yet...we (especially in the US) are still expected to pay inflated drug prices for meds that are often pretty old, unoriginal, and only moderately effective, at best. Great system.
American drugs are too expensive!
~Ed
Posted by zeugma on October 21, 2005, at 17:59:37
In reply to Re: Triple reuptake inhibitors and MAOIs » med_empowered, posted by ed_uk on October 21, 2005, at 14:16:55
Hi Med!
>And yet...we (especially in the US) are still expected to pay inflated drug prices for meds that are often pretty old, unoriginal, and only moderately effective, at best. Great system.
American drugs are too expensive!
~Ed
Agreed, Ed.
Now why isn't Prothiaden out in America yet? It may be old, unoriginal, and only as effective as amitriptyline, but I would bet my money that it would be more effective than a triple reuptake inhibitor.
And it does have one of the best names of any AD
:-)
-z
Posted by Iansf on October 21, 2005, at 18:51:58
In reply to Re: Triple reuptake inhibitors and MAOIs » ed_uk, posted by zeugma on October 21, 2005, at 17:59:37
> Now why isn't Prothiaden out in America yet? It may be old, unoriginal, and only as effective as amitriptyline, but I would bet my money that it would be more effective than a triple reuptake inhibitor.
>
> And it does have one of the best names of any AD
>
I don't recall hearing Prothiaden mentioned before, or is there a generic name that may be more familiar? What are the specifics of Prothiaden?
Posted by ed_uk on October 22, 2005, at 15:38:20
In reply to Re: Triple reuptake inhibitors and MAOIs » ed_uk, posted by zeugma on October 21, 2005, at 17:59:37
Hi Z,
>Now why isn't Prothiaden out in America yet?
I don't think it was ever marketed in America. I don't know why. Not long ago, it was the most popular AD in England, a lot of people still take it (well, the generic, hardly anyone takes Prothiaden). GPs are being discouraged from prescribing Prothiaden at the moment, it's very toxic in overdose.
You'll never see Prothiaden in the US Zeugie, it's just too old..... and much too cheap.
At the pharmacy, when we buy dothiepin from the wholesaler, a box of 28 dothiepin 25mg caps costs us about £1.00
>And it does have one of the best names of any AD
I like it too :-)
~Ed
Posted by ed_uk on October 22, 2005, at 15:39:45
In reply to Re: Triple reuptake inhibitors and MAOIs » zeugma, posted by Iansf on October 21, 2005, at 18:51:58
Hi
The generic name for Prothiaden is dothiepin (now dosulepin). It's a sedating TCA, similar to amitriptyline (Elavil).
~ed
This is the end of the thread.
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