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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 Jimmyboy on January 4, 2007, at 13:42:08
I keep reading that these are going to be the big deal in the future, but aren't combo's that are already give the same effect. Like combining an SSRI + Bupropion - seems like you hit all 3 there - S NE and DA.
Don't MAOI's do that too? Effect all 3 that is..
What about supplements like SAM-e , I think that effects all 3 also..
Just wondering if there is something I'm missing here
JB
Posted by blueberry1 on January 4, 2007, at 14:36:35
In reply to Triple Re-uptake inhibitors- why so excited?, posted by Jimmyboy on January 4, 2007, at 13:42:08
I think all the drugs work in such complicated ways, especially at molecular levels that are not recognized or understood versus the overall effect they do. For example, I sometimes wonder if it is those unrecognized things that does the healing and that, say for example with ssris, it is the serotonin reuptake that gives the side effects but not the healing. That could explain why 4 ssris won't work for someone but a 5th will be a miracle...it wasn't lack of serotonin, it was something else unique to the drug.
The drugs all act in different parts of the brain, with varying intensity in those different parts, and they have an impact on how genes talk to each other, how receptors talk to each other, calcium, magnesium, potassium currents, and all kinds of weird stuff that I do not understand. And likely the high powered scientists don't understand either.
The idea of a triple reuptake inhibitor is in my opinion a grasp at more profits but not necessarily more healing. I would bet a new triple reuptake inhibitor would have about the same clinical efficacy as anything else (not great) and probably more side effects. Just a hunch though.
Since parnate and nardil basically do the same thing, then why will one work great and the other not? Or neither works at all?
And it is my humble opinion that most of us do not have a lack of serotonin or other neuros. I think the whole idea of marinating a brain in high density neurotransmitters is flawed. If it was accurate, then all someone would need to do is take 5htp and tyrosine supplements. A triple reuptake inhibitor just takes that whole flawed theory one step further. The ultimate goal is a new profit generator.
These opinions of mine are highly debateable I realize. I'm very glad that some people do find their meds to be miracles. And I'm very glad there will be new ones to offer the same potential. I am afraid though that any new one, based on old theories, will be a blockbuster in sales but not a blockbuster in actual reliable healing.
I do not mean to sound skeptical so please don't take it that way. I just think they need brand new blockbuster theories in the causes of depression, not new versions of old drugs.
Posted by Quintal on January 4, 2007, at 14:40:30
In reply to Triple Re-uptake inhibitors- why so excited?, posted by Jimmyboy on January 4, 2007, at 13:42:08
>Don't MAOI's do that too? Effect all 3 that is..
That's something I've been thinking myself, but the MAOIs aren't reuptake inhibitors as such. The main advantage of the triple reuptake inhibitors over the MAOIs obviously will be the lack of dietary and medication restrictions. Reducing the number of meds taken also benefits the patient (hopefully) in terms of fewer side effects.
I think you're right though in many ways these will be used as new toys to play with by a certain group of pdocs and their sycophants alike.
Q
Posted by linkadge on January 4, 2007, at 15:19:11
In reply to Re: Triple Re-uptake inhibitors- why so excited? » Jimmyboy, posted by Quintal on January 4, 2007, at 14:40:30
I think there would be advantages in that a person could get a more even effect on ser nor dopamine. Wellbutrin is a very weak dopamine uptake inhibitor, so to get dopamine reuptake in the same magnitude as the other monoamines would be very diffuclt.
Thought, I don't know the difference between a triple uptake inhibitor and cocaine. And the withdrawl from a TRI would probably make effexor hell look like a trip to Hannah Barbarra Land.
Linkadge
Posted by Quintal on January 4, 2007, at 15:36:13
In reply to Re: Triple Re-uptake inhibitors- why so excited?, posted by linkadge on January 4, 2007, at 15:19:11
>Thought, I don't know the difference between a triple uptake inhibitor and cocaine. And the withdrawl from a TRI would probably make effexor hell look like a trip to Hannah Barbarra Land.
It's closer to the action of 'crystal meth' which is a triple reuptake inhibitor itself. I was thinking of mentioning this in an earlier thread to when somebody objected to the use of opiates in depression. It seems we are getting closer to mimicking the actions of drugs of abuse with some of the new antidepressants and radical approaches (i.e. buprenorphine).
Q
Posted by djmmm on January 4, 2007, at 15:39:28
In reply to Triple Re-uptake inhibitors- why so excited?, posted by Jimmyboy on January 4, 2007, at 13:42:08
> I keep reading that these are going to be the big deal in the future, but aren't combo's that are already give the same effect. Like combining an SSRI + Bupropion - seems like you hit all 3 there - S NE and DA.
>
> Don't MAOI's do that too? Effect all 3 that is..
>
> What about supplements like SAM-e , I think that effects all 3 also..
>
> Just wondering if there is something I'm missing here
>
>
> JBIt is very interesting... treatment seems to be cyclical in nature. The first antidepressants being not very selective at all, to drugs like Celexa which are highly selective-- then to drugs like effexor (reminiscent of the TCA's), the reemergence of the MAOIs (deprenyl), and even simple stimulants (like strattera)-- and NOW triple re-uptake inhibitors... I think changes in treatment options are primarily due to "trends" rather than efficacy.
Posted by SLS on January 4, 2007, at 16:17:12
In reply to Triple Re-uptake inhibitors- why so excited?, posted by Jimmyboy on January 4, 2007, at 13:42:08
> I keep reading that these are going to be the big deal in the future,
I don't know about them being such a big deal, but they will offer an interesting alternative to experiment with.
> but aren't combo's that are already give the same effect.
No. There are no potent dopamine reuptake inhibitors currently available.
> Like combining an SSRI + Bupropion - seems like you hit all 3 there - S NE and DA.
Bupropion is a weak reuptake inhibitor at best. With the exception of Sheldon Preskorn, MD, I don't know of many psychopharmacologists willing to attribute the clinical therapeutic effects of bupropion to reuptake inhibition. I haven't kept up with it, but I think the thought on bupropion is that it ultimately produces an increase in noradrenergic neurotransmission through some yet to be determined set of mechanisms.
> Don't MAOI's do that too? Effect all 3 that is..
The key probably lies in the details of what, where, and how.
> Just wondering if there is something I'm missing here
I'm sure there is something we are all missing, including the neuroscientists. That's why I think we should keep an open mind and remain at least moderately optimistic. I find that cynicism bears very little edible fruit. (Not directed at you) Of course, constructive criticism is an entirely different tree to cultivate, especially when positive actions are taken in an attempt to improve a situation.
I guess I would like to see something radically different from reuptake inhibitors prove themselves effective and come to market quickly. Because of my history of responding only briefly to the reuptake inhibitors, I can't help but to assume that I need a drug with mechanisms of action that are very much different. But I'll try the triple-reuptake-inhibitors when they come out and remain hopeful that I will respond to them. It will be interesting to see what happens.
As I usually state, I think it is in our best interest to have more tools to work with, not less. Each tool does not have to be a miracle drug for all. It just needs to be a miracle drug for some.
- Scott
Posted by SLS on January 4, 2007, at 16:27:13
In reply to Triple Re-uptake inhibitors- why so excited?, posted by Jimmyboy on January 4, 2007, at 13:42:08
I forgot to acknowledge Blueberry1's post. It is very insightful and probably explains a great deal as to the inconsistency between the intraindividual and interindividual clinical effects of drugs that we generally categorize as being similar. One SSRI does not fit all.
- Scott
Posted by linkadge on January 4, 2007, at 16:55:17
In reply to Re: Triple Re-uptake inhibitors- why so excited? » linkadge, posted by Quintal on January 4, 2007, at 15:36:13
>It's closer to the action of 'crystal meth' >which is a triple reuptake inhibitor itself
I didn't know methamphetamine had affinity for the serotonin transporter.
Linkadge
Posted by linkadge on January 4, 2007, at 16:59:44
In reply to Re: Triple Re-uptake inhibitors- why so excited? » Jimmyboy, posted by SLS on January 4, 2007, at 16:27:13
The only think is, that not all dopamine reuptake inhibitors have abuse potential.
Cocaine may be different in that it affects the release of monoamines in addition to affecting their reuptake.
Just like how MDMA, is a serotonin reuptake inhibitor, but that doesn't mean SSRI's have
the abuse potential that MDMA has.Another point is that SJW is a triple uptake inhibitor, with moderate but equal potency on the three monoamines. SJW has no abuse potential though, and is not comparable to cocaine.
So, I don't know if the these "similarities" would mean the drugs are similar in abuse potential.
Linkadge
Posted by Phillipa on January 4, 2007, at 21:50:15
In reply to Re: Triple Re-uptake inhibitors- why so excited?, posted by linkadge on January 4, 2007, at 16:59:44
So let me get this right one med would target serotonin, dopamine, and norepenephrine? Love Phillipa ps how bout one that targets Gaba too?
Posted by djmmm on January 5, 2007, at 9:37:59
In reply to Re: Triple Re-uptake inhibitors- why so excited?, posted by Phillipa on January 4, 2007, at 21:50:15
> So let me get this right one med would target serotonin, dopamine, and norepenephrine? Love Phillipa ps how bout one that targets Gaba too?
I think Nardil is the only med that covers all the above :)
Posted by Quintal on January 5, 2007, at 10:37:03
In reply to Re: Triple Re-uptake inhibitors- why so excited?, posted by linkadge on January 4, 2007, at 16:55:17
>I didn't know methamphetamine had affinity for the serotonin transporter.
Nor did I until a few weeks ago but it does, although weakly:
__________________________________________________Methamphetamine also indirectly prevents the reuptake of these neurotransmitters, causing them to remain in the synaptic cleft for a prolonged period. Serotonin levels are only weakly affected (ratio NE: DA = 2:1, NE:5HT = 60:1).
http://en.wikipedia.org/wiki/Methamphetamine
__________________________________________________Q
Posted by Quintal on January 5, 2007, at 10:58:21
In reply to Re: Triple Re-uptake inhibitors- why so excited?, posted by linkadge on January 4, 2007, at 16:59:44
>Just like how MDMA, is a serotonin reuptake inhibitor, but that doesn't mean SSRI's have
the abuse potential that MDMA has.Well it seems MDMA is a bit more than an SSRI:
__________________________________________________MDMA (3,4-methylenedioxy-N-methylamphetamine), most commonly known by the street names Ecstasy, E, X, or XTC is a semisynthetic entactogen of the phenethylamine family, whose primary effect is believed to be the stimulation of secretion as well as inhibition of re-uptake of large amounts of serotonin as well as dopamine and norepinephrine in the brain, inducing a general sense of openness, empathy, energy, euphoria, and well-being.
http://en.wikipedia.org/wiki/MDMA
__________________________________________________
>Another point is that SJW is a triple uptake inhibitor, with moderate but equal potency on the three monoamines. SJW has no abuse potential though, and is not comparable to cocaineSounds a bit like Nardil:
__________________________________________________Some believe that Hyperforin is the major constituent responsible for antidepressant activity, and it has been shown to inhibit the uptake of 5-HT, dopamine, noradrenaline, GABA and glutamate.
http://en.wikipedia.org/wiki/St_John%27s_Wort
__________________________________________________I've never taken Nardil but I know I was able to abuse Parnate as a euphoric stimulant at high doses.
I'm sure abuse potential will be carefully screened in the clinical trials but that wasn't really the point I was trying to make. It just seems we're taking a step closer to the pharmacology of many substances of abuse in our quest for more effective antidepressants, regardless of whether these substances will have abuse potential themselves.
Ronald K. Siegel, Ph.D. makes this point in his book "Intoxication: the universal drive for mind altering substances"
Q
Posted by linkadge on January 5, 2007, at 12:14:11
In reply to Re: Triple Re-uptake inhibitors- why so excited? » linkadge, posted by Quintal on January 5, 2007, at 10:58:21
So, I guess thats a good distinction. Parnate and Nardil are both inhibitors of MAOa/b, but parnate has some abuse potential while nardil doesn't seem to have documented abuse potential.
So, I think its possable to develop a triple uptake inhibitors with little abuse potential.Linkadge
Posted by TenMan on January 5, 2007, at 13:16:44
In reply to Re: Triple Re-uptake inhibitors- why so excited?, posted by linkadge on January 5, 2007, at 12:14:11
I'm sure someone out there is working on a synthetic derivative of Hyperforin which hopefully will lack the pesky affinity for PXR.
Posted by linkadge on January 5, 2007, at 13:43:33
In reply to Re: Triple Re-uptake inhibitors- why so excited?, posted by TenMan on January 5, 2007, at 13:16:44
Yeah, synthetic hyperforin could be a very usefull tool.
Linkadge
Posted by djmmm on January 5, 2007, at 18:43:07
In reply to Re: Triple Re-uptake inhibitors- why so excited?, posted by linkadge on January 5, 2007, at 12:14:11
> So, I guess thats a good distinction. Parnate and Nardil are both inhibitors of MAOa/b, but parnate has some abuse potential while nardil doesn't seem to have documented abuse potential.
>
>
> So, I think its possable to develop a triple uptake inhibitors with little abuse potential.
>
>
>
> Linkadge
>
>
>
>Parnate differs in that it has catecholamine releasing properties... perhaps that's why it can be abused?
i'll try to find journal abstracts supporting this..
Posted by Phillipa on January 5, 2007, at 18:56:34
In reply to Re: Triple Re-uptake inhibitors- why so excited?, posted by djmmm on January 5, 2007, at 9:37:59
It does? Nardil targets Gabba? No wonder ED_uk always says I should try it. Thanks Love Phillipa
Posted by djmmm on January 5, 2007, at 19:16:24
In reply to Re: Triple Re-uptake inhibitors- why so excited? » djmmm, posted by Phillipa on January 5, 2007, at 18:56:34
> It does? Nardil targets Gabba? No wonder ED_uk always says I should try it. Thanks Love Phillipa
sure does.. it's major metabolite phenylethylidenehydrazine increases GABA levels
Posted by Quintal on January 5, 2007, at 19:39:06
In reply to Re: Triple Re-uptake inhibitors- why so excited?, posted by djmmm on January 5, 2007, at 19:16:24
>sure does.. it's major metabolite phenylethylidenehydrazine increases GABA levels
I've wondered for a while if the GABAergic effect of 'phenylethylidenehydrazine' made Nardil feel more like a barbiturate or a benzo?
PsychoBabble's Ace described Nardil as having an 'overall deadening effect' which sounds more like my experiences with barbs rather than benzos. I wonder if this makes Nardil a kind of all-in-one upper/downer? The catecholamine enhancing effects provide stimulation while the raised GABA levels act as a downer?
Q
Posted by Phillipa on January 5, 2007, at 20:18:48
In reply to Re: Triple Re-uptake inhibitors- why so excited? » djmmm, posted by Quintal on January 5, 2007, at 19:39:06
I surely may be mistaken am a lot but didn't Ace at one time add seroquel? I wonder why? Love Phillipa Wish he would post more and stick around. I do have his e-mail.
Posted by Quintal on January 6, 2007, at 13:15:19
In reply to Re: Triple Re-uptake inhibitors- why so excited? » Quintal, posted by Phillipa on January 5, 2007, at 20:18:48
I don't know Phillipa. He was talking about adding Risperdal a few weeks ago to help with the anxiety I think, yet he claimed Nardil was still 99% effective as an anxiolytic.
Q
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