Friday, September 14, 2007

Does Pagoclone fight the symptoms?

I found this interesting 1998 report on Pagoclone here:
Interneuron Pharmaceuticals, Inc. (NASDAQ: IPIC) today announced results of a Phase 2/3 trial showing that treatment with pagoclone, a novel GABA receptor modulator, statistically significantly reduced the frequency of panic attacks among patients suffering from panic disorder
Putting on the stuttering glasses, the stuttered speech is very often made worse due to the panic that kicks in at blocks. I often feel being out-of-control during my speech, unable to slow down, and then I have even more blocks. According to the study, Pagoclone reduces the frequency of panic attacks, and this effect might very well happen in people who stutter during their speech. They are less likely to get into a panic or the panic will be less severe, thereby giving the person more control of his or her speech, which in turn decreases the probability of blocks.

This would suggest that Pagoclone doesn't act and therfore doesnt tell us anything about stuttering itself (i.e. why do they have many more blocks than fluent speakers?), but reduces the panic secondary symptoms leading to more control and less stuttering.


Greg said...

Tom--it seems that you're assuming that Pagaclone only does 1 thing. And that one thing is to reduce panic (fight/flight).

I could only wish that these types of neuroleptics could be so targeted and precise--but they're not. They're like shotgun blasts to the brain; you may hit the target, but you've also tinkered with everything around it.

To the best of my knowledge, Pagaclone reduces GABA activity, which in turn reduces Dopaminergic activity. Reduction in D2 activity allows the basil ganglia to function more similarly to that of a fluent person. (i.e., increasing performance in the medial pathway.) This indirect methodology to reduce D2 may be why the side-effects are so much more tolerable.

The fact that Pagaclone may have anti-anxiety or anti-panic results is merely icing on the cake.

Tom Weidig said...

I dont assume anything at all. I look at the empirically measured effect of panic frequency reduction. Therefore I bypass all theoretical speculation, as I only look at the effect. And I speculate on how this effect could impact on a stutterer's speech.

"Reduction in D2 activity allows the basil ganglia to function more similarly to that of a fluent person. (i.e., increasing performance in the medial pathway.)"

This sounds like you know why stuttering occurs; a too high D2 activity which Pagoclone reduces. This is speculative. Wait, I thought you said that stuttering might NOT be a speech disorder? :-)

>>The fact that Pagaclone may have anti-anxiety or anti-panic results is merely icing on the cake.

I am not saying Pagoclone could not have the effect you are speculating on. I am saying that its panic-reducing effect can very well explain all the supposedly seen benefits from the trials. If Pagoclone has additional effects like on fluency itself, I would expect stronger treatment effects.

Greg said...

We'd get some pretty good banter over beers, no doubt about it. Let me know if you're ever at one of the bigger US SLP events.

It sounds like you know the literature well enough--which would mean that you know that during stuttering moments, cellular activity levels (and D2 levels) get all wonky, including that within the BG.

So this isn't to say that errors in BG processing is the cause of stuttering, but an associated phenomenon with it. And you know as well as I that select D2 antagonists appear to address this issue, at least to some degree. Thus, addressing wonky BG functioning appears to help w/ stuttering severity (and stuttering frequency, albeit to a lesser extent). I never said D2 levels are a cause; to think that would be really, really dumb.

And to get back to that stuttered speech disorder thing... Stuttering appears to be a disorder causing disruptions in expressive lingustic output. Thus, it's not a speech disorder; it is just most often observed or manifested in speech output.

But yeah--it's difficult to tease out the effect from Pagaclone. Is it reductions in D2 or reductions in anxiety? (Although other anti-anxiety drugs have been tried w/ mixed results.)

But in a sense--who cares. At least it's got potential to be a new stuttering treatment in the near-term, which may lead to bigger & better things down the road.

Anonymous said...

Is it possible to even figure out why just one person stutters--what that one person's brain chemistry, different brain areas are involved. Perhaps the best way to unweave this is to get to really know the "why" of one person at a time.