pregabalin and its activity?

[Bare_head]

Hey guys,

I recently have been diagnosed too have asd , i have been self medicating for years and now i have stopped most drugs barr weed and clonazepam, which i will come too later..

Anyways the specialist has perscribed me 75mg twice a day of pregabalin, i would like u clever folk if anyone knows its activity on what receptors it works on other than its a gaba working drug? Anyone found it effective personally? I know it will have a cross tolerance with the clonazepam i am taking, which brings me to my next question..

Does anyone have the receptor activity in studies on clonazepam? Im interested to know both for pregabalin and clonazepam really, im trying to taper the clonazpeam and jus want to know if the pregab is gonna help with the withdrawls?

 

[sekio]

Pregabalin doesn't have activity at GABA-A or B, it's instead a voltage gated calcium channel modulator.

Clonazepam is a GABA-A positive allosteric modulator.

I don't think the two will neccesarily substitute for each other, although the pregabalin will probably help with the symptoms of w/d from benzos, by other means.

 

[Bare_head]

thanks for clearing that up seiko, do you know how etizolam works compared to clonazepam, i know its not a benzo outright but i am interested to know why clonazepam doesnt really have any sort of sedative effect on me where as etizolam/temazepam/valium (to a certain extent) all really work well as a sleep aid? is there some kind of difference in how these work on the GABA-A/B receptors?

so where does pregabelins psychoactive effects come from, what is this drug working on if it has no gaba activity? i am reading about voltage-dependent calcium channels, i really think i should have stuck in at chemistry at school now ha! i am finding a real dry mouth at the moment aswell as cramps in my legs from 75mg, it did have some kind of effect earlier on.. strange chemical to say the least.

i did mange only 1mg of clonazepam last night which is good i normally take 2mg/1.5, that drug is a real strange one, its the only benzo i dont really enjoy but it keeps me flat calm, where as other benzos like diazepam / temazepam all give me euphoria and are much more sedative, im already way over my head here =)

 

[irobeth]

Pregabalin doesn't have activity at GABA-A or B, it's instead a voltage gated calcium channel modulator.

Clonazepam is a GABA-A positive allosteric modulator.

I don't think the two will neccesarily substitute for each other, although the pregabalin will probably help with the symptoms of w/d from benzos, by other means.

Since the VGCC binding decreases glutamate release should it also result in upregulation of the gaba receptor after continued use? I used pregabalin daily for a long long time and definitely noticed a withdrawal (i.e. rebound excitotoxicity) effect that necessitated tapering when i quit

 

[sekio]

Since the VGCC binding decreases glutamate release should it also result in upregulation of the GABA receptor after continued use?

No, that doesn't follow.

Also, on some benzos being "recreational" and others not: I think it has to do with whether or not they are N-methylated benzos or triazolo compounds (.e.g temazepam, alprazolam, etizolam) or not (desmethyldiazepam, clonazepam, phenazepam). There are several subtypes of the GABA-A receptor that banzos can bind to with varying specificities.

 

[irobeth]

re: pregabalin and GABA, I'm looking for literature now and this is all I can find so far:

http://www.ncbi.nlm.nih.gov/pubmed/11709066

Upregulation of gamma-aminobutyric acid transporter expression: role of alkylated gamma-aminobutyric acid derivatives.

Pregabalin [(S)-(+)-3-isobutylgaba] and gabapentin [1-(aminomethyl)cyclohexane acetic acid] are gamma-aminobutyric acid (GABA) derivatives that are effective in the treatment of behavioural disorders, convulsions, epilepsy and hyperalgesia. The mechanisms underlying the diverse actions of these compounds in the brain have not been well elucidated. To test the hypothesis that these compounds exert some of their effects on GABAergic systems in the brain, we examined their role in regulating the rat brain GABA transporter GAT1, a plasma membrane protein involved in regulating synaptic transmitter levels. Prolonged incubation of hippocampal cultures, which endogenously express GAT1, with gabapentin and pregabalin caused a 2-fold increase in subsequent GABA uptake, which was concentration- and time-dependent. This increase in uptake was correlated with a redistribution of GAT1 protein from intracellular locations to the plasma membrane. Further experiments also suggested that the signal transduction cascade that modulates pregabalin-mediated GAT1 redistribution may involve pathways activated by specific GAT1 substrates and antagonists but does not involve protein kinase C and tyrosine kinases, two other pathways known to regulate GAT1 redistribution. These data suggest that pregabalin and gabapentin may exert some of their actions in the brain by altering GABAergic signalling.