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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 43. This is the beginning of the thread.
Posted by ravenstorm on July 3, 2005, at 17:56:33
Does anybody know how the following two drugs are suppossed to help with anxiety/depression? How would there side effects profiles differ from the drugs available now?
SR 58611: beta-3-adrenoceptor agonist
saredutant, SR 48968: NK2 antagonist.
If you do know what the above means, if you could state it in a fairly easy to understand translation I would appreciate it!
Posted by linkadge on July 3, 2005, at 18:15:44
In reply to How do these drugs work? In phase III trials, posted by ravenstorm on July 3, 2005, at 17:56:33
I think the NK2 antagonist is a substance P antagonist.
These drugs seem to block the activity of substance P, which I believe, is a form of neurotransmitter that transmits signals of pain (presubably both emotional and physical pain)
Linkadge
Posted by Shawn. T. on July 3, 2005, at 23:07:47
In reply to How do these drugs work? In phase III trials, posted by ravenstorm on July 3, 2005, at 17:56:33
Substance P has a low affinity (which results in low potency) for NK2 receptors. Neurokinin A is the high affinity agonist for NK2 receptors that is naturally present in the body. So NK2 antagonists like saredutant primarily interfere with the effects of neurokinin A. Substance P and neurokinin A are called tachykinins; this group also includes neurokinin B, neuropeptide K, and neuropeptide gamma. They're all likely to have some affinity for NK2 receptors.
One of the key substances involved in anxiety and depression is CRF. This peptide acts to modulate physiological processes in the brain and body during stressful situations. Part of this role involves increasing the release of certain neurotransmitters in various regions of the brain. Researchers have found that NK2 receptor antagonists such as saredutant can reduce the CRF-induced release of norepinephrine in the prefrontal cortex and acetylcholine in the hippocampus (see the two links below). Thus, they believe that some of the effects of CRF on neurotransmitter release may involve a CRF-induced increase in neurokinin A. These researchers have also found that NK2 antagonists increase CREB levels in the hippocampus after long term treatment; this is an effect shared by most antidepressant drugs. In addition, they found that NK2 antagonists reduce stress-induced substance P release.
http://jpet.aspetjournals.org/cgi/content/full/299/2/449
Also, NK2 antagonists may inhibit the HPA axis:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9663462
The take home message here is that the mechanism of action of saredutant (SR 48968) suggests that it is perhaps the most promising drug in phase II or phase III clinical trials for anxiety and depression. The drug is currently in phase III in the US, and Sanofi-Synthelabo claims that the phase IIb results were "very promising."
I'm not sure about the role that beta-3-adrenoceptors might play in depression. All I can tell you is that they are activated by norepinephrine.
Shawn
Posted by ravenstorm on July 4, 2005, at 10:55:29
In reply to Saredutant looks like a winner, posted by Shawn. T. on July 3, 2005, at 23:07:47
Posted by ravenstorm on July 4, 2005, at 10:56:38
In reply to Saredutant looks like a winner, posted by Shawn. T. on July 3, 2005, at 23:07:47
Thanks for the information. Do you think these drugs will have less side effects than SSRIs?
Posted by Shawn. T. on July 4, 2005, at 12:49:26
In reply to Re: How many years until these hit the market? (nm), posted by ravenstorm on July 4, 2005, at 10:55:29
According to Reuters on June 6, "Dresdner Kleinwort Wasserstein expects saredutant to enter the market in the second half of 2007 and foresees sales of $3.1 billion by 2010."
Shawn
Posted by Shawn. T. on July 4, 2005, at 13:24:04
In reply to Re: Saredutant looks like a winner, posted by ravenstorm on July 4, 2005, at 10:56:38
According to Schoor et al. (1998) in a study involving 12 mild asthmatics, "Saredutant was biologically and clinically well tolerated and no serious events were noted. Two non serious events were noted: patients number 7 and 11 both experienced mild frontal headache on the active treatment day; in both cases it subsided spontaneously until complete recovery." That's not much information, but I strongly doubt that saredutant will have more side effects than SSRIs. I don't know enough about SR 58611 to speculate about it.
Shawn
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9701408
Posted by ravenstorm on July 4, 2005, at 14:34:13
In reply to Saredutant looks like a winner, posted by Shawn. T. on July 3, 2005, at 23:07:47
How would you find out about where they are doing clinical trials on this drug?
In clinical trials, do you get to take the drug for more than four to six weeks? Or are you shoved out the door at that point?
Posted by linkadge on July 4, 2005, at 15:23:04
In reply to Saredutant looks like a winner, posted by Shawn. T. on July 3, 2005, at 23:07:47
Researchers have found that NK2 receptor antagonists such as saredutant can reduce the CRF-induced release of norepinephrine in the prefrontal cortex and acetylcholine in the hippocampus (see the two links below).
----------------------------------------------Depressing as these actions may be. I'm not sure if I'd want to be taking this drug before a school exam.
Linkadge
Posted by linkadge on July 4, 2005, at 15:25:11
In reply to Re: Saredutant looks like a winner, posted by linkadge on July 4, 2005, at 15:23:04
Ie. The stress induced increase in frontal cortex norepinephrine, and hippocampal acetylcholine sounds like its putting your brain into a "taking care of buisness" mode.
Linkadge
Posted by Shawn. T. on July 5, 2005, at 0:27:06
In reply to Re: Saredutant looks like a winner, trials?, posted by ravenstorm on July 4, 2005, at 14:34:13
>How would you find out about where they are >doing clinical trials on this drug?
I don't know. Maybe you could e-mail someone at Sanofi-Aventis.
>In clinical trials, do you get to take the drug >for more than four to six weeks? Or are you >shoved out the door at that point?
Sometimes you do; sometimes you don't. I believe that long-term studies are more commonly performed after a drug has been launched.
Shawn
Posted by Shawn. T. on July 5, 2005, at 0:58:20
In reply to Re: Saredutant looks like a winner, posted by linkadge on July 4, 2005, at 15:25:11
In general, the brain can best take care of business when extracellular neurotransmitter levels are neither too low nor too high. An increase in the activation of alpha-1-adrenoceptors by norepinephrine in the prefrontal cortex can result in stress-induced cognitive deficits.
An article in Science by Amy Arnsten (1998) called "The Biology of Being Frazzled" addressed this point:
"These studies emphasize the importance of dopamine D1 receptor actions in taking the prefrontal cortex 'off line' during stress. Other neuromodulators may contribute as well [for example, norepinephrine via a1-adrenoceptors (14)], ensuring rapid yet reversible loss of prefrontal cortical control over behavior.
This bimodal reaction to stress likely had survival value in evolution: Under stress, the faster, habitual, or instinctual mechanisms regulated by the amygdala, hippocampus, striatum, and posterior cortices would control behavior, and long-lasting memories of aversive stimuli would be enhanced in order to avoid such stimuli in the future. However, in modern human society these brain actions may often be maladaptive; now we need prefrontal cortex regulation to act appropriately."
I wouldn't use the same language to describe this phenomenon, but she is basically explaining why excess neurotransmitter levels are not always a good thing.
Shawn
Posted by ravenstorm on July 5, 2005, at 8:52:34
In reply to Re: Saredutant looks like a winner » linkadge, posted by Shawn. T. on July 5, 2005, at 0:58:20
Posted by linkadge on July 5, 2005, at 15:37:03
In reply to Re: Saredutant looks like a winner » linkadge, posted by Shawn. T. on July 5, 2005, at 0:58:20
I suppose "excess" is not a good thing. THe problem is that feeling comfortable, is not aways the most adaptive state of mind.
Linkadge
Posted by Denise1966 on July 6, 2005, at 7:33:20
In reply to Re: How many years until these hit the market? (nm), posted by ravenstorm on July 4, 2005, at 10:55:29
.
Posted by ravenstorm on July 6, 2005, at 9:52:48
In reply to Ravenstorm,You make me smile,like me so impatient, posted by Denise1966 on July 6, 2005, at 7:33:20
Posted by Denise1966 on July 6, 2005, at 12:11:30
In reply to Re: Denise, did you ever contact nemifitimide? (nm), posted by ravenstorm on July 6, 2005, at 9:52:48
Hi Ravenstorm.
I've added the update to our original discussion on Nemifitide.
Denise
Posted by utopizen on July 6, 2005, at 14:43:40
In reply to Saredutant looks like a winner, posted by Shawn. T. on July 3, 2005, at 23:07:47
I remember Phil Donahue a couple of years ago on MSNBC talking with Magic Johnson, and mentioning something about "It's gotten much better since back when they only had those terrible Substance P drugs with all those side effects, hasn't it?" and Magic concurred.
How is this different?
Posted by Shawn. T. on July 6, 2005, at 15:31:28
In reply to Substance P's: poorly-tolerated HIV drugs?, posted by utopizen on July 6, 2005, at 14:43:40
Saredutant does not block the high affinity receptor for substance P.
Shawn
Posted by cncgordon on September 4, 2005, at 1:30:30
In reply to Re: Substance P's: poorly-tolerated HIV drugs?, posted by Shawn. T. on July 6, 2005, at 15:31:28
I am taking part in the Saredutant study. I have so many questions and the only information you can find is how a rat reacts to having their neck rubbed or when they are exposed to a cat. I feel like such a lab rat it isn't funny. Will let you know how things go.
Posted by cncgordon on September 4, 2005, at 1:36:41
I am in the phase3 study of saredutant. I am hoping to find others that are participating in the study as well. I figure it will be like finding a needle in a hay stack but worth a try.
If anyone has any other information besides how mice react to having thier necks scatched or how a rat reacts to being put face to face with a cat then please feel free to e-mail me.
Posted by Phillipa on September 4, 2005, at 19:03:40
In reply to saredutant study, posted by cncgordon on September 4, 2005, at 1:36:41
What in the world is it? Fondly, Phillipa
Posted by cncgordon on September 5, 2005, at 9:16:05
In reply to Re: saredutant study, posted by Phillipa on September 4, 2005, at 19:03:40
It is a new drug to treat depression.
Posted by Phillipa on September 5, 2005, at 16:09:40
In reply to Re: saredutant study, posted by cncgordon on September 5, 2005, at 9:16:05
Thanks so much. What country is it in? Fondly, Phillipa
Posted by cncgordon on September 6, 2005, at 9:21:33
In reply to Re: saredutant study » cncgordon, posted by Phillipa on September 5, 2005, at 16:09:40
It's a world wide study. I believe there are only 250 people in this phase of the study but I could be wrong.
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