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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 5 of 5. This is the beginning of the thread.
Posted by Maxime on June 16, 2003, at 11:08:03
I was in the hospital in December for a med change. I meet a guy there who was bipolar 2. He was part of the clinical trials for pregabalin. I looked it up on the internet and I couldn't find any trials that were done for Bipolar 2 - only fibromyalgia (sp?)and anxiety.
I was just wondering if anyone on this board was involved in clinical trials of the drug Pregabalin.
The guy in the hospital told me it was the best thing he had ever been on because of the low side effect profile.
I know that pregabalin is supposed to be related to Neurotin in some way so I can see where it would be used for anxiety and as a mood stabiliser.
So has anyone tried it? Does anyone have any information on the drug?
Max
Posted by Larry Hoover on June 16, 2003, at 11:53:49
In reply to Trials for pregabalin, posted by Maxime on June 16, 2003, at 11:08:03
> I know that pregabalin is supposed to be related to Neurotin in some way so I can see where it would be used for anxiety and as a mood stabiliser.
>
> So has anyone tried it? Does anyone have any information on the drug?
>
> MaxGabapentin, 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.
Posted by Maxime on June 16, 2003, at 12:25:25
In reply to Re: Trials for pregabalin » Maxime, posted by Larry Hoover on June 16, 2003, at 11:53:49
Thanks for the information Larry. Oh I hope it becomes available soon. Maybe it will be the answer for me. :-)
Max
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.
Posted by Larry Hoover on June 16, 2003, at 14:32:42
In reply to Re: pregabalin and Ca-channels » Larry Hoover, posted by Ritch on June 16, 2003, at 13:30:54
> 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.That would have been my answer. ;-)
>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").
I don't think you can draw generalities, simply because two compounds share the theoretical construct CCB (calcium channel blockade). Not all CCBs have psychoactive effects, and studies of the interaction of CCBs show that even those acting on a common receptor class must bind at different positions and have different effects, as some interact by increasing activity, and some interact by decreasing activity, relative to a single CCB at the receptor.
>Is it that verapamil has more of a "shotgun" effect and pregabalin is simply more selective?
They're both selective. They just select differently.
The anti-manic effect of verapamil was discovered by serendipity. It's not like they set out to regulate calcium channels in the brain. Verapamil works better if taken with magnesium, itself a regulator of calcium channels.
Calcium channels et al are not really something I feel expert about. There are numerous different types of them, and even the same receptor type may be regulated differently in different tissues/organs.
> Or is it something completely different? I've always wondered about this. Thanks for any help.
I'm going to conclude with a big shrug, okay? You pays your money and you takes your chances.
Lar
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