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A couple questions about Pregabalin

mitragyna

mitragyna

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Dec 7, 2006
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I've always been curious how Pregabalin (and Gabapentin) actually work as an anxiolytic. From what I've read:
Like gabapentin, pregabalin binds to the α2δ (alpha2delta) subunit of the voltage-dependent calcium channel in the central nervous system. This reduces calcium influx into the nerve terminals and decreases the release of neurotransmitters such as glutamate, noradrenaline and substance P (Australian Medicines Handbook).
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Doesn't Pregabalin indirectly affect Gaba in the brain? And if so, how would binding to this calcium channel (like quoted) go about this? I'm basically just looking for someone to clarify the quote (assuming it's correct).

EDIT: Another question: I know that Gabapentin has a sort of "ceiling dose", in that you just start pissing it out when you reach a certain dose. Also, the more you take the less BA.

With that said - I'm assuming the same is with Pregabalin - correct? At what dose does your body stop absorbing it?

Thanks!
 
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No, it's not the same for pregabalin. gabapentin is transported by some amino acid transporter, pregabalin isn't- it's taken up in a more normal fashion (from the gut this is).

I don't think there's any evidence it actually buggers with GABA.
 
Pregabalin is a substituted GABA analog and does affect GABAergic action in the brain fwiw...

Basically think of it as calming the brain down. "Reducing calcium influx" is essentially a fancy way of saying "slowing down your brain chemicals." Fewer calcium ions going back and forth means fewer neurotransmitters going around, which means less anxiety, less epileptic behavior, etc.

I just started taking this stuff today, and goddamn.... my anxiety is much improved already, but I feel completely trashed... It definitely slows you down...
 
rant*N*rave said:
Pregabalin is a substituted GABA analog and does affect GABAergic action in the brain fwiw...

Basically think of it as calming the brain down. "Reducing calcium influx" is essentially a fancy way of saying "slowing down your brain chemicals." Fewer calcium ions going back and forth means fewer neurotransmitters going around, which means less anxiety, less epileptic behavior, etc.

I just started taking this stuff today, and goddamn.... my anxiety is much improved already, but I feel completely trashed... It definitely slows you down...
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Nothing you said is useful at all. There are DA analogues that have no dopaminergic effect, the fact that it's an analogue is irrelevant. It does not bind to any GABA receptor or allosteric sites.
 
Gabapentin and pregabalin definitely have indirect effects on GABA pathways... try drinking alcohol on gabapentin -- they certainly interact like a mo'fucka!!
 
Opiates also strongly interact with alcohol despite no GABAergic nature. That's a faulty argument.
 
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neverstop said:
^Don't listen to this guy, he only has 116 posts what could he possibly know?
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HAH! I'm worried people actually think that, though. before I could say things and people would believe me- I mean, I'm right, but my post count carried an added authority. Now newbs argue with me :(
 
For me, pregabalin has been very helpful against my social anxiety - before I could not function properly at work because of so high levels of anxiety (I was a supermarket clerk) but after getting a prescription for pregabalin the social anxiety was majorly reduced. The whole problem with interaction with customers and fellow workers was minimized. Now 6 months later I still feel it has helped me in my life as a whole. If I only had had access to this 10 years ago ....


A problem might be that dosage upping will probably be necessary in steps over a couple of months. But it has a very high ceiling of recommended maximum dosage.

It seems to be very gentle in the addictive department, I have never felt any problem with stopping taking it during vacations or some such. Have friends who have had endless supply of this medication and in that case clearly habituation and abuse developed which was hard to stop, with unpleasant mental and bodily effects following for a week. This was in regards to very high dosages.

In higher dosages, reminding of GHB. And as noted earlier in thread, interacts with alcohol, just be careful!

It has a slow onset, which I solve by setting my alarm clock a couple of hours before work, taking my dosage, and when I arrive at work a fuzziness and slight clumsiness of mind, not wholly unpleasant, and a markedly more easily spoken me has emerged.

Sometimes I augment with a high dosage of L-theanine (+1g) which potentiates the experience.
 
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pregabalin is AFAIK a gaba agonist, and yeah, most gaba analogs are atleast to some extent. Neurontin is also a gaba/glutamte aswell as alcohol. Anyway, i think I read that in a pamphlet a docs office. I took a bunch of lyricas with some ketamine and that shot knocked me the fuck out, I was sleeping sitting up(not in a k hole) just hammered. Pfizer does say it doesnt effect it tho which is weird
 
what's substance P? Isn't that the drug from that movie with keanu reeves as a cartoon?(forgot the name-(brain fart))

nevermind. i answerd my own Q. a substance P inhibitor, that means that lyrica would be a better anti-emetic than anyother common antiemetics out there right? better than dramamine,domperidone,5ht3/2c antagonists...

^^but gaba(along with other simple amino) is such a simple structure that changing it could lead to just about any kind of activity or lack there of
 
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Pregabalin and Gabapentin are not GABA agonists

ref: Pregabalin: From molecule to medicine

European Neuropsychopharmacology, Volume 16, Supplement 2, July 2006, Pages S128-S133
Richard Kavoussi View Abstract
 
^^
Great link. Pregabalin seems like the perfect drug for anxiety. Sure, it's a little addictive, but certainly less than benzos. And it seems to work better than benzos IMO. It doesn't have that "dulling" effect on me like they do, works great on my depression.

So I'm assuming the mechanism of action in the link posted above is the same action of Gabapentin? Just to a lesser and limited extent?
 
^^ It seems to mostly affect calcium channels, and it's not really a very good GABA agonist. That's not to say, however, that it's completely without activity on GABA receptors. This article claims it's able to affect post-synaptic GABAb receptors on glutamatergic neurons, but doesn't affect GABAb receptors on GABA neurons. That means that it selectively slows excitatory responses without enhancing inhibitory ones.


I like the title of the paper: Not another Gabapentin mechanism!
 
I dont know about all this gabaa gabab what-not, but ive been on it for years and i can tell you that it is my favorite anxiolytic. its a very clean subtle but defiantly noticable feeling. unlike benzos, where you dont have anxiety because your just fucked up and dont care.
 
TRPPNASS_DSCOMONKE said:
I dont know about all this gabaa gabab what-not, but ive been on it for years and i can tell you that it is my favorite anxiolytic. its a very clean subtle but defiantly noticable feeling. unlike benzos, where you dont have anxiety because your just fucked up and dont care.
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What dosage did you start out on? and what dosage are you on now?
 
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