Posted by Ritch on June 16, 2003, at 13:30:54
In reply to Re: Trials for pregabalin » Maxime, posted by Larry Hoover on June 16, 2003, at 11:53:49
> Gabapentin, when used as a mood stabilizer, is off-label, so I wouldn't be surprised to find this drug used that way as well.
>
> Expert Opin Investig Drugs. 2003 Apr;12(4):663-72.
>
> Pregabalin: a new anxiolytic.
>
> Lauria-Horner BA, Pohl RB.
>
> Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
>
> Pregabalin (S-[+]-3-isobutylgaba) was designed as a lipophilic GABA (gamma-aminobutyric acid) analogue substituted at the 3'-position in order to facilitate diffusion across the blood-brain barrier. It was originally developed as an anticonvulsant agent, however it has been shown to be effective in the treatment of several disorders including hyperalgesia and behavioural disorders. Although its exact mode of action remains unclear, pregabalin interacts with the same binding site and has a similar pharmacological profile as its predecessor, gabapentin (1-[aminomethyl] cyclohexane acetic acid). Its main site of action appears to be on the alpha(2)delta subunit of voltage-dependent calcium channels, widely distributed throughout the peripheral and central nervous system. Pregabalin appears to produce an inhibitory modulation of neuronal excitability. In healthy volunteers, it is rapidly absorbed with peak blood concentrations within 1 h and it has a bioavailability of approximately 90%. In preclinical trials of anticonvulsant activity, pregabalin is three to ten times more potent than gabapentin. It is well-tolerated and associated with dose-dependent adverse effects (ataxia, dizziness, headache and somnolence) that are mild-to-moderate and usually transient. There are no known pharmacokinetic drug-drug interactions reported to date. Preliminary animal and human studies showed beneficial effects in both ethological and conflict models of anxiety, as well as having some sleep-modulating properties. In Phase II and III trials, pregabalin shows promising anxiolytic action when compared to placebo in generalised anxiety disorder, social phobia and panic disorder.
>
Larry, I've used Neurontin with great success before for anxiety and sleep (especially). But, I get this weird side effect from it where my thoracic chest wall muscles tend to tighten and spasm causing chest pain, etc. We don't know why this happens, but I'm not on it now. I miss the stuff a lot because it worked so well with my Depakote and I *ALWAYS* slept so well on it. Do you think that gabapentin and pregabalin are so similar that this side effect will probably recurr with the newer med? That's probably impossible to predict-I'd have to try it and see I suppose. Anyhow my main question has to do with "voltage-dependent Calcium channels". There are CCB drugs like verapamil that my pdoc has brought up once, and SusanC here has had good results with it(plus Depakote) for rapid cycling bipolar. How is the action of verapamil (used for cardiac arrthymia and angine) different from the action of pregabalin ("alpha(2)delta subunit of voltage-dependent calcium channels"). Is it that verapamil has more of a "shotgun" effect and pregabalin is simply more selective? Or is it something completely different? I've always wondered about this. Thanks for any help.
poster:Ritch
thread:234311
URL: http://www.dr-bob.org/babble/20030614/msgs/234352.html