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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 20 of 20. This is the beginning of the thread.
Posted by jrbecker on September 27, 2005, at 8:20:32
DOV Pharmaceutical, Inc. Announces Phase II Efficacy Results for One of its Novel Antidepressants, DOV 216,303
http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/09-27-2005/0004132415&EDATE=
Neurosearch to start phase 3 tests of depression treatment NS2359 next yearhttp://www.forbes.com/markets/feeds/afx/2005/09/23/afx2240564.html
Triple reuptake inhibitors will inherit depression market
http://www.drugresearcher.com/news/news-ng.asp?id=61172-antidepressant-glaxosmithkline-merck
For more compounds in development, see...
Posted by iforgotmypassword on September 27, 2005, at 8:38:24
In reply to Triple Reuptake Inhibitors - Race to Market, posted by jrbecker on September 27, 2005, at 8:20:32
not to be cynical again, but i am very skeptical that anything actually dopaminergic will ever hit the market.
Posted by SLS on September 27, 2005, at 10:30:32
In reply to Re: Triple Reuptake Inhibitors - Race to Market, posted by iforgotmypassword on September 27, 2005, at 8:38:24
> not to be cynical again, but i am very skeptical that anything actually dopaminergic will ever hit the market.
Nomifensine (Merital) hit the market in the 1980s. It was a reuptake inhibitor of both dopamine and norepinephrine that was very effective as an antidepressant. For some people, it was the only drug they ever responded to. There was no hint of substance abuse potential with nomifensine. It was voluntarily removed from the worldwide market when reports of fatal hemolytic anemia began to appear. I have no idea what the true statistical occurance of this condition was.
As long as people continue to insist that Wellbutrin works by inhibiting the reuptake of dopamine, I think DA reuptake inhibitors will be offered as potential antidepressants.
- Scott
Posted by linkadge on September 27, 2005, at 15:37:52
In reply to Re: Triple Reuptake Inhibitors - Race to Market, posted by SLS on September 27, 2005, at 10:30:32
Dispite the theories of serotonin in depression, most SSRI's have an underlying dopaminergic mechanism.
One study showed that a d2 blocker abolished the AD effect of SSRI's wheras it did not induce depression in normals.
A triple uptake inhibitor would be nice. I responded well to SJW. I think its hypeforin, (or hypercin) is a triple uptake inhibitor.
If effexor truely does have a higher responce rate than SSRI's, then it stands to reason that broader specrum may be superior.
Linkadge
Posted by linkadge on September 27, 2005, at 15:40:33
In reply to Re: Triple Reuptake Inhibitors - Race to Market, posted by SLS on September 27, 2005, at 10:30:32
I don't get the whole abuse potential thing either. If we can treat hyperactive children with abusable drugs, then why is it inconcievable to treat depression with a drug that may cary an abuse potential?
Linkadge
Posted by jclint on September 27, 2005, at 15:43:56
In reply to Re: Triple Reuptake Inhibitors - Race to Market, posted by linkadge on September 27, 2005, at 15:37:52
Don't the MAOIs do this already?
Posted by jay on September 27, 2005, at 15:44:28
In reply to Re: Triple Reuptake Inhibitors - Race to Market, posted by SLS on September 27, 2005, at 10:30:32
> > not to be cynical again, but i am very skeptical that anything actually dopaminergic will ever hit the market.
>I am also skeptical, as I honestly am not convinced dopamine reuptake inhibition is really what is needed.
To me, I am of the thought that depression and anxiety are two heads of the same coin. It is interesting that they now have revealed Anxiety as a symptom as being linked to Bipolar and even Schizophrenia. That is why I have more faith in the area of dopamine/serotonin *modulation*...or best yet...*balance*.. than anything. Also, each of the different subtypes of receptors need to be explored. I really thought we where going in the right direction with meds like Serzone possibly combined with an SNRI/SRI, as well as combos involving Abilify and Zyprexa, and even the older often-bashed, Buspar. On top of this, the benzos seem to be the *ultimate* meds that bring balance...especially to the anxiety producing effects of antidepressants.
So, we need a massive plethora of agonists and antagonists that work at a multitude of receptor sites. We must go beyond looking at some simple model that says we simply need to increase *this* or *that* NT. I feel it is the receptor subtypes that will lead us in the direction to tackle more specific symptoms. We should go beyond just *topping up* on dopamine, or serotonin (where did that get us?), etc.
IMHO...respectfully
Jay
Posted by linkadge on September 27, 2005, at 16:26:19
In reply to Re: Triple Reuptake Inhibitors - Race to Market » SLS, posted by jay on September 27, 2005, at 15:44:28
I agree with most of what you are saying. There is more need for ballance. A triple uptake inhibitor may help people who would otherwise seem to respond to MAOI's
OTOH, I find that psychiatrists modify what their diagnostic criteria based on which drugs work. Ie, antidepressants don't help your anxiety?, Then you must be bipolar or have schitsophrenia. They never seem to consider the possabiltiy that their drugs are simply inadequate.
A triple uptake inhibitor may offer more ballance. And it might be a better building block to add on specific agonists antagonists.
Linkadge
Posted by SLS on September 27, 2005, at 17:22:15
In reply to Re: Triple Reuptake Inhibitors - Race to Market, posted by linkadge on September 27, 2005, at 15:40:33
> I don't get the whole abuse potential thing either. If we can treat hyperactive children with abusable drugs, then why is it inconcievable to treat depression with a drug that may cary an abuse potential?
>
> Linkadge
I agree.If a drug is therapeutic for a medical condition, it is nice to have it available.
It is the responsibility of the physicians to properly prescribe such drugs and for the pharmacies to properly fill the prescriptions. Abuse of this system is punishable by law and liable to civil actions.
Cocaine is still manufactured legally and is available as a prescription drug. So is methamphetamine.
The rest is for the drug enforcement agencies to worry about.
I never had the chance to try amineptine.
- Scott
Posted by Ktemene on September 27, 2005, at 17:59:24
In reply to Triple Reuptake Inhibitors - Race to Market, posted by jrbecker on September 27, 2005, at 8:20:32
Posted by med_empowered on September 27, 2005, at 18:09:19
In reply to Re: Triple Reuptake Inhibitors - Race to Market, posted by SLS on September 27, 2005, at 17:22:15
Psychiatry is rife with contradictions...one the one hand, shrinks give 11 year olds amphetamines...then people who are afraid to leave their houses pop in, and they might be given antipsychotics and pat on the back, when benzos could do the job much better (and more safely). But...they're "abusable". **Sigh**. In other parts of medicine...in the US at least, the DEA is cracking down on anybody and everybody who dares to cross their line of what's acceptable. Pain docs who seem to overprescribe--even if their "excessive prescribing" helps the vast majority of patients--are coming under fire. Even in the hospice/palliative care area of medicine, the DEA is putting "drug abuse prevention" above the needs and comfort of patients..and doctors, instead of following their oaths to serve the **patient**, have largely rolled over and allowed this to happen. Its a shame, really. Anyway, that whole anti-drug, anti-fun mentality carries over into psychiatry--how else can you explain the tremendous success of antipsychotics (quite possibly the most anti-fun, anti-pleasure drugs imaginable) for off-label uses? Look at amineptine (Survector). Effective--very effective. Yes, there were some problems with liver issues (mostly in those who overused it). But...this is also true of Depakote, Lithium, and many cholesterol lowering drugs; those drugs, of course, are still on the market. But..since amineptine made people feel good and some people overused it, it was pulled. What does that say about our mentality towards psychiatric drugs? Drugs shouldn't make you feel good--they should quiet voice, calm anxiety, get you to work and school on time, but they should never, ever, make you feel *good* ? Its ridiculous..and punitive. It seems that often psychiatry isn't about *treating* problems; its about reducing your level of suffering so you can participate in the economy without causing undue problems or killing yourself. *sigh* Anyway, I hope somebody develops worthwhile antidepressants with fewer side effects..and I hope this time around shrinks demand more and better data before spraying these new drugs around and blaming patients when they fail (b/c with the SSRIs, it was always the patient's "failure to respond" not the medication's "failure to do SOMETHING")
Posted by Phillipa on September 27, 2005, at 19:23:38
In reply to Abuse Potential, posted by med_empowered on September 27, 2005, at 18:09:19
Med, good post but you still didn't turn on your babblemail. Ed explained how. Don't you like personal responses? Fondly, Phillipa
Posted by KaraS on September 27, 2005, at 19:32:41
In reply to Triple Reuptake Inhibitors?Like high-dose Effexor? (nm), posted by Ktemene on September 27, 2005, at 17:59:24
Hopefully more balanced. High-dose Effexor is still primarily serotonergic with very little dopamine reuptake.
Posted by Chairman_MAO on September 27, 2005, at 21:51:32
In reply to Triple Reuptake Inhibitors - Race to Market, posted by jrbecker on September 27, 2005, at 8:20:32
If you take tranylcypromine at 120mg/day or more, you are taking a triple uptake inhibitor:
para-Hydroxytranylcypromine (p-OHTCP) has recently been unequivocally identified in our laboratory as a metabolite of the antidepressant tranylcypromine (TCP). In the study reported here, we have determined brain and heart levels of p-OHTCP in the rat after intraperitoneal administration of a 0.1 mmol/kg dose of TCP or N-(2-cyanoethyl)tranylcypromine (CE-TCP). The animals were killed at 5, 15, 30, 60, 120 or 240 min after drug administration and the tissues (brain and heart) rapidly dissected out. The tissues were frozen in isopentane on solid carbon dioxide and stored at -20 degrees C until time of analysis. Tissue levels of p-OHTCP, TCP and CE-TCP were determined after aqueous pentafluorobenzoylation by conducting analyses with a gas-liquid chromatograph equipped with a fused silica (SE-54) capillary column and an electron-capture detector. Our results show that substantial concentrations of p-OHTCP were present in both brain and heart after TCP and CE-TCP administration. Higher levels of p-OHTCP were present in the brain than in the heart after TCP treatment, but this situation was reversed with the CE-TCP-treated rats. Since p-OHTCP has been shown to retain some MAO-inhibiting properties and to have effects on uptake of catecholamines and serotonin it could therefore contribute to the pharmacological profile of TCP.
I wish they'd throw that drug in a patch, man. ;)
BTW: My doctor switched me back to tranylcypromine 120mg/day + Lunesta because I just couldnt take phenelzine anymore (complete inability to have sex). At least I have a hip enough doctor that he doesnt have a problem with giving me 12 tabs per day. Too bad my lunesta script is only 1mg, but he said we can titrate up. I just want to sleep!
What would be really cool is if I had enough sedation to allow me to take the TCP at bedtime. Then I could maintain steady state plasma levels at all times of the metabolitse. rockin'
P.S. My phenylethylidenehydrazine synth is coming along. We need some input tho: the freebase cannot survive the stomach and is an oil. Making a decent salt is hard. any other ideas?
Posted by KaraS on September 28, 2005, at 6:43:59
In reply to Re: Triple Reuptake Inhibitors?Like high-dose Effexor? » Ktemene, posted by KaraS on September 27, 2005, at 19:32:41
> Hopefully more balanced. High-dose Effexor is still primarily serotonergic with very little dopamine reuptake.
I meant very little dopamine reuptake inhibition.
Posted by iforgotmypassword on September 28, 2005, at 10:27:18
In reply to Re: Triple Reuptake Inhibitors - Race to Market » jrbecker, posted by Chairman_MAO on September 27, 2005, at 21:51:32
wow! i didn't know you could just switch like that! :P
god with the properties of that metabolite i worry if Parnate could induce it's own serotonin syndrome by itself. does the metabolite actually reach effective significant levels when you take parnate?
Posted by Declan on September 28, 2005, at 17:18:55
In reply to Re: Triple Reuptake Inhibitors - Race to Market » jrbecker, posted by Chairman_MAO on September 27, 2005, at 21:51:32
So is the choice either you 're depressed, or you do without sex, or you do without sleep?
I hope Lunesta cuts it for you, but I have my doubts.
Declan
Posted by linkadge on September 28, 2005, at 18:11:07
In reply to Abuse Potential, posted by med_empowered on September 27, 2005, at 18:09:19
Thats exactly it. Parnate comes close to an abusable drug, and many psychiatrists are uncomfortable with its properties for this reason.
But the dumb thing, is that we are throwing the baby out with the bath water.There may be the best drugs out there that cure the deepest treatment resistant depression unresponsive to other drugs, but if the drugs give the slightest high to normals, then you will never see the drug again.
Linkadge
Posted by Cecilia on September 29, 2005, at 1:51:34
In reply to Triple Reuptake Inhibitors - Race to Market, posted by jrbecker on September 27, 2005, at 8:20:32
Race to market? My observation of the approval process of psychotropic drugs is that it resembles a race between an elderly turtle and a sick slug. Cecilia
Posted by denise1966 on September 29, 2005, at 10:50:47
In reply to Re: Triple Reuptake Inhibitors - Race to Market, posted by Cecilia on September 29, 2005, at 1:51:34
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This is the end of the thread.
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