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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 15 of 15. This is the beginning of the thread.
Posted by Jaynee on February 23, 2002, at 14:53:38
I have read lots on Gepirone and Pagoclone. Interested in any new information on these two drugs. Mostly whether or not they are close to being approved.
Thanks
Posted by paulb on February 26, 2002, at 17:22:50
In reply to Any new info on Gepirone or Pagoclone, posted by Jaynee on February 23, 2002, at 14:53:38
Some good, info was posted on the latest on Pagoclone a short while here ago at Bobbys, an article now only two months old following the progress of the Pagoclone pill:
Direct link to article:
http://news.moneycentral.msn.com/category/industryarticle.asp?feed=BW&Date=2001It is an extremely lengthy business to get a drug approved by the FDA requiring Phase 1,2 and 3 trials but if your interested in following the latest drug developments go to the site itself:
http:www.fda.gov
Also http://www.abpi.org.uk follows the development of medications and Pagoclone Im sure would be under the anxiety section.
Pfizer seems to be working with Interneuron Pharmaceuticals on Pagoclone but Neurogen seem to be leading the way with new anxiolytics. A visit to their site will reveal more.....
http://www.neurogen.com
Hope this helps
paulb
Posted by Elizabeth on February 28, 2002, at 1:43:07
In reply to Any new info on Gepirone or Pagoclone, posted by Jaynee on February 23, 2002, at 14:53:38
> I have read lots on Gepirone and Pagoclone. Interested in any new information on these two drugs. Mostly whether or not they are close to being approved.
I don't know about that, but if you're interested in trying gepirone, you might consider high-dose Buspar. They're very similar drugs, and Buspar acts as an antidepressant in high doses (around 45-90 mg). (It's quite safe; Buspar was originally studied as an antipsychotic, and although it was completely ineffective, doses over 1 g were well tolerated.)
Pagoclone looks interesting, but I have a hard time coming up with a justification for taking an expensive name-brand drug when I could get a generic benzodiazepine much more cheaply.
-elizabeth
Posted by JohnX2 on March 1, 2002, at 5:34:51
In reply to Re: Any new info on Gepirone or Pagoclone, posted by Elizabeth on February 28, 2002, at 1:43:07
I'll be waiting in the Pagoclone line with my wallet open.
Hopefully I'll be off my Klonopin addiction by then.
Why do I suck so much at these habit forming medicines?-John
> > I have read lots on Gepirone and Pagoclone. Interested in any new information on these two drugs. Mostly whether or not they are close to being approved.
>
> I don't know about that, but if you're interested in trying gepirone, you might consider high-dose Buspar. They're very similar drugs, and Buspar acts as an antidepressant in high doses (around 45-90 mg). (It's quite safe; Buspar was originally studied as an antipsychotic, and although it was completely ineffective, doses over 1 g were well tolerated.)
>
> Pagoclone looks interesting, but I have a hard time coming up with a justification for taking an expensive name-brand drug when I could get a generic benzodiazepine much more cheaply.
>
> -elizabeth
Posted by SLS on March 1, 2002, at 10:20:13
In reply to Re: Any new info on Gepirone or Pagoclone, posted by Elizabeth on February 28, 2002, at 1:43:07
> I don't know about that, but if you're interested in trying gepirone, you might consider high-dose Buspar. They're very similar drugs, and Buspar acts as an antidepressant in high doses (around 45-90 mg). (It's quite safe; Buspar was originally studied as an antipsychotic,
and although it was completely ineffective, doses over 1 g were well tolerated.)
Hi Elizabeth.It is my recollection (dubious, of course) that buspirone was originally investigated as an antidepressant. One thing that seems to escape people's attention is that the primary metabolite (1-PP?) of buspirone and the other azapirones (gepirone, ipsapirone) is a potent NE alpha-2 antagonist as is Remeron. I'm wondering to what degree this contributes to its antidepressant properties. My spelling might be off.
- Scott
Posted by Lorraine on March 6, 2002, at 19:46:45
In reply to Re: Any new info on Gepirone or Pagoclone » Elizabeth, posted by SLS on March 1, 2002, at 10:20:13
According to this site, the method of action of Buspar is believed to be that it reduces serotonin.
Lorraine
Posted by JohnX2 on March 7, 2002, at 2:33:05
In reply to Re: Buspar reduces serotonin, posted by Lorraine on March 6, 2002, at 19:46:45
I've looked into buspar mechanism.
This medicine never made sense to me!
On the one hand it tries to relieve anxiety
by mitigating hyperactive serotonin conductance
in a key area of the noggin.But then it has this side metabolite that Scott
was talking about that blocks this "alpha-2"
noradrenaline receptor that indirectly increases
the serotonin cunductance on the exact same path!No wonder this drug does no wonders for some
people, (IMHO).-John
> According to this site, the method of action of Buspar is believed to be that it reduces serotonin.
>
> http://www.buspar.com
>
> Lorraine
Posted by Lorraine on March 7, 2002, at 17:41:57
In reply to Re: Buspar reduces serotonin, posted by JohnX2 on March 7, 2002, at 2:33:05
Posted by Frankie on March 7, 2002, at 20:47:05
In reply to Re: Buspar reduces serotonin, posted by Lorraine on March 6, 2002, at 19:46:45
> According to this site, the method of action of Buspar is believed to be that it reduces serotonin.
>
> http://www.buspar.com
>
> Lorraine
Lorraine,Both of you are correct. Buspar does lower serotonin overabundance in the brain. But, this could be a good thing, in augmentation with an SSRI. You see, the SSRI's all elevate, or block the uptake of serotonin, enabling it to remain in the part of the brain where it is most active, and does the most good. And, supposedly, GAD (generalized anxiety disorder), or the series of mind racing thoughts day in and day out, is due to an overproduction of serotonin. So, in reality, Buspar will work over time to slow the racing mind. However, it also has a weak affinity for dopamine also. It brings it up a bit. So, it is possible to actually get jittery from it. Just until you adjust. It is a unique medicine. It is very expensive if you were to pay full price for it. I believe that it is one of the most expensive medications out there period! So, it is not worthless. It's actions are a mystery to most, including me, and most professionals. But, I encourage you to stay on it, especially if you have GAD. The dose is better low though, because many that take a high dose get a bit of hostility from it. I think it is the combination of the lowering of the S1 serotonin receptor, plus the elevation of a certain dopamine receptor. Good luck.
Frankie.
Posted by JohnX2 on March 7, 2002, at 21:55:00
In reply to Re: Buspar reduces serotonin, posted by Frankie on March 7, 2002, at 20:47:05
Right, for GAD, I would think the recommended
lower dose of 30 mg sufficient.It's my understanding that the extra metabolite
that block the "alpha-2" noradrenaline receptor
boosting noradrenaline, indirectly increases
serotonin conductance, and counter attacks
the soothing affect of the primary workhorse that
reduces sertonin shooting.
The extra metabolite really kicks in
at the highest doses (60 mg).So at the higher dose it can be more irritating,
but this extra noradrenergic affect gives it some
anti-depressant boost. Right?-John
> > According to this site, the method of action of Buspar is believed to be that it reduces serotonin.
> >
> > http://www.buspar.com
> >
> > Lorraine
>
>
> Lorraine,
>
> Both of you are correct. Buspar does lower serotonin overabundance in the brain. But, this could be a good thing, in augmentation with an SSRI. You see, the SSRI's all elevate, or block the uptake of serotonin, enabling it to remain in the part of the brain where it is most active, and does the most good. And, supposedly, GAD (generalized anxiety disorder), or the series of mind racing thoughts day in and day out, is due to an overproduction of serotonin. So, in reality, Buspar will work over time to slow the racing mind. However, it also has a weak affinity for dopamine also. It brings it up a bit. So, it is possible to actually get jittery from it. Just until you adjust. It is a unique medicine. It is very expensive if you were to pay full price for it. I believe that it is one of the most expensive medications out there period! So, it is not worthless. It's actions are a mystery to most, including me, and most professionals. But, I encourage you to stay on it, especially if you have GAD. The dose is better low though, because many that take a high dose get a bit of hostility from it. I think it is the combination of the lowering of the S1 serotonin receptor, plus the elevation of a certain dopamine receptor. Good luck.
>
> Frankie.
Posted by SLS on March 8, 2002, at 7:13:22
In reply to Re: Buspar reduces serotonin, posted by Frankie on March 7, 2002, at 20:47:05
I thought the following article appearing on Medscape would be helpful along this thread. Please forgive me if my posts are little more than copy-and-paste. It might be worth noting that buspirone and its sister drugs, gepirone, and ipsapirone, are serotonin 5-HT1a autoreceptor agonists (partial). Here, buspirone is acting like "fake" serotonin at the same site that the article describes as needing to be downregulated for SSRIs to exert their therapeutic antidepressant effects. Perhaps some neurons need an extra kick in the ass. This might account for buspirone's reputation as being effective as an augmentor of antidepressants, but not in monotherapy. It occurs to me that a full 5-HT1a antagonist like pindolol would mask these autoreceptors and thus virtually "downregulate" them and produce the desired dynamics prior to the two week latency necessary for this to occur naturally. This might account for pindolol's reputation as being able to accelerate antidepressant response.
Understanding What Antidepressants Dohttp://www.medscape.com/viewarticle/418726
- Scott
--------------------------------------------
<excerpt>Understanding What Antidepressants Do
"Pierre Blier, MD, PhD, of the University of Florida at Gainesville discussed the biological effects of antidepressant molecules on neurotransmitters and receptors. He began by looking closely at selective serotonin reuptake inhibitors (SSRIs) and how these drugs impact the serotonin system.[4]
Dr. Blier reviewed the regulation of the brain's serotonin system. The cell bodies of the serotonin neurons are located in the brainstem, mostly in the median and dorsal raphe nuclei. Projections from these two nuclei reach multiple brain structures. He illustrated the activities of the serotonin (5-HT)-1A autoreceptor and the 5-HT uptake transporter. He explained that when the 5-HT-1A receptor is stimulated by an increase in the amount of serotonin, it will decrease the firing activity of the serotonin neurons.
When an SSRI is introduced, initially there is an increase in serotonin levels at the cell body due to blockade of the 5-HT uptake transporter. The 5-HT-1A autoreceptors are stimulated and decrease the firing frequency of the neuron. Yet, at the level of the synaptic bouton, there is no marked increase in serotonin availability, even though the transporters are inactive, because the firing activity reaching the terminals is decreased. However, after a few weeks of treatment with the SSRI, the autoreceptors are desensitized and allow a recovery of firing activity. At the synaptic bouton, reuptake is still blocked, firing activity is restored, and there is more serotonin because the terminal autoreceptors are desensitized. This allows 5-HT neurons to release their transmitters without negative feedback action in the presence of reuptake inhibition. The time necessary to obtain these adaptive changes is consistent with the delayed onset of action of SSRIs in major depression."
Posted by Lorraine on March 9, 2002, at 12:52:36
In reply to Re: Buspar reduces serotonin - article, posted by SLS on March 8, 2002, at 7:13:22
I want to thank all of you who have posted, Frankie, JohnX2 and Scott. I feel like I have the lay of the land so to speak. I'm taking Buspar with Provigil--which is not an SSRI. I have SSRI--they always make me feel worse and aggitated. I'm taking Klonopin and Neurontin with the Provigil (25 mg), but was hoping to cut the Klonopin and swap in Buspar if it works. I am not a long term Klonopin user, just 3 weeks now and three weeks about a month ago. I love Klonopin, but think it contributes to sinusitus and hair loss for me. And, yes, I'm very sensitive to drugs. I was on Buspar before, highest dose 10 mg 2x day, but at the time I was on Effexor, which is anxiolytic, so my only comment was that it was prosexual mildly. We'll see, it is day 8.
Lorraine
Posted by JohnX2 on March 10, 2002, at 4:47:45
In reply to Re: Buspar using with Provigil, posted by Lorraine on March 9, 2002, at 12:52:36
Good Luck Lorraine!Took both. Low side effects. ;)
-John
> I want to thank all of you who have posted, Frankie, JohnX2 and Scott. I feel like I have the lay of the land so to speak. I'm taking Buspar with Provigil--which is not an SSRI. I have SSRI--they always make me feel worse and aggitated. I'm taking Klonopin and Neurontin with the Provigil (25 mg), but was hoping to cut the Klonopin and swap in Buspar if it works. I am not a long term Klonopin user, just 3 weeks now and three weeks about a month ago. I love Klonopin, but think it contributes to sinusitus and hair loss for me. And, yes, I'm very sensitive to drugs. I was on Buspar before, highest dose 10 mg 2x day, but at the time I was on Effexor, which is anxiolytic, so my only comment was that it was prosexual mildly. We'll see, it is day 8.
>
> Lorraine
Posted by lansolut on June 5, 2002, at 8:00:42
In reply to Re: Any new info on Gepirone or Pagoclone » Elizabeth, posted by JohnX2 on March 1, 2002, at 5:34:51
I don't know when it will be approved but I'm in a Phase III study (the extended release version) and it's a very good drug. It lifts depression and, to a lesser degree, anxiety. There are vitually no side effects other than some very minor ones at startup - which go away after a few days.
The only problem with it (and this could just be me) is that when it wears off in the evening, the anxiety comes back. Can't take more at night because it can cause insomnia.
> I'll be waiting in the Pagoclone line with my wallet open.
> Hopefully I'll be off my Klonopin addiction by then.
> Why do I suck so much at these habit forming medicines?
>
> -John
>
>
> > > I have read lots on Gepirone and Pagoclone. Interested in any new information on these two drugs. Mostly whether or not they are close to being approved.
> >
> > I don't know about that, but if you're interested in trying gepirone, you might consider high-dose Buspar. They're very similar drugs, and Buspar acts as an antidepressant in high doses (around 45-90 mg). (It's quite safe; Buspar was originally studied as an antipsychotic, and although it was completely ineffective, doses over 1 g were well tolerated.)
> >
> > Pagoclone looks interesting, but I have a hard time coming up with a justification for taking an expensive name-brand drug when I could get a generic benzodiazepine much more cheaply.
> >
> > -elizabeth
Posted by JohnX2 on June 5, 2002, at 16:15:58
In reply to Re: Any new info on Gepirone or Pagoclone, posted by lansolut on June 5, 2002, at 8:00:42
Thanks for the followup.Don't you think the medicine would be helpful to
wean benzo addicts off their meds?Regards,
John
> I don't know when it will be approved but I'm in a Phase III study (the extended release version) and it's a very good drug. It lifts depression and, to a lesser degree, anxiety. There are vitually no side effects other than some very minor ones at startup - which go away after a few days.
>
> The only problem with it (and this could just be me) is that when it wears off in the evening, the anxiety comes back. Can't take more at night because it can cause insomnia.
>
>
>
> > I'll be waiting in the Pagoclone line with my wallet open.
> > Hopefully I'll be off my Klonopin addiction by then.
> > Why do I suck so much at these habit forming medicines?
> >
> > -John
> >
> >
> > > > I have read lots on Gepirone and Pagoclone. Interested in any new information on these two drugs. Mostly whether or not they are close to being approved.
> > >
> > > I don't know about that, but if you're interested in trying gepirone, you might consider high-dose Buspar. They're very similar drugs, and Buspar acts as an antidepressant in high doses (around 45-90 mg). (It's quite safe; Buspar was originally studied as an antipsychotic, and although it was completely ineffective, doses over 1 g were well tolerated.)
> > >
> > > Pagoclone looks interesting, but I have a hard time coming up with a justification for taking an expensive name-brand drug when I could get a generic benzodiazepine much more cheaply.
> > >
> > > -elizabeth
This is the end of the thread.
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