Psycho-Babble Medication Thread 626479

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Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk

Posted by yxibow on April 3, 2006, at 14:58:55

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please! » Sobriquet Style, posted by ed_uk on April 3, 2006, at 13:53:18

> Hi
>
> Have you ever tried chlordiazepoxide (Librium)? Chlordiazepoxide is easier to taper than most benzos (similar to diazepam). The advantage of chlordiazepoxide is that it apparantly has a lower 'street value' than the other benzos......and so your doc may be more comfortable prescribing it.
>
> Chlordiazepoxide is not a good PRN benzo, it doesn't 'kick in' as quickly as Xanax or Valium. It is, however, a logical choice if a benzo is to be taken daily for several weeks or more.
>
> As with all anxiolytic benzos, it's efficacy beyond 4 months is unclear.
>
> Regards
>
> Ed
>
> PS. How do you like clonazepam (Klonopin, Rivotril)?
>


Librium is like about 1/10 of the resulting potency of Valium, which is why Valium became the default when Librium was released around 1959-1960 and Valium became the seller in 1962. Librium is still used for alcohol detox, I guess primarily because its so weak that abuse by patients would be inhibited. Valium doesnt have, at least in the US anyway, nearly the street value of Xanax, and Klonopin I doubt has much at all.

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » yxibow

Posted by ed_uk on April 3, 2006, at 15:20:23

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk, posted by yxibow on April 3, 2006, at 14:58:55

Hi Yxi

>Librium is like about 1/10 of the resulting potency of Valium

Diazepam is about 4 times more potent than chlordiazepoxide. In the treatment of anxiety, the usual maximum dose of chlordiazepoxide is 100mg per day ie. about 25mg diazepam - which is probably an adequate dose for most people. Chlordiazepoxide comes in 5mg, 10mg and 25mg capsules. Chlordiazepoxide is not a good choice for people who require high doses of benzodiazepines.

>its so weak

It's ideal for people who respond well to low doses of benzodiazepines. Also, the 5mg capsules are very convenient for tapering.

>abuse by patients would be inhibited

Chlordiazepoxide has a gradual onset, it doesn't suddenly 'kick in'. This may result in a lower recreational value. Doctors see this as a bonus.

>alcohol detox

It's used a lot for detox here in the UK. If it really was so 'weak' it wouldn't be useful for detox.

>Valium became the default when Librium was released around 1959-1960 and Valium became the seller in 1962

I think Librium was popular for a long time.

Regards

Ed

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk

Posted by Phillipa on April 3, 2006, at 21:53:34

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » yxibow, posted by ed_uk on April 3, 2006, at 15:20:23

Well no wonder it didn't work when I originally started on valium in the 70's. The doc tried to switch me to librium but nothing. Back to valium. It does lose it's relaxing properties over the years but they last for a lot of years not months. I'll be the rat that is the test subject. Love PJ O

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk

Posted by yxibow on April 4, 2006, at 1:15:17

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » yxibow, posted by ed_uk on April 3, 2006, at 15:20:23


> Diazepam is about 4 times more potent than chlordiazepoxide. In the treatment of anxiety,

5, http://en.wikipedia.org/wiki/Diazepam, and http://www.dr-bob.org/tips/bzd.html, though we won't quibble :)

> I think Librium was popular for a long time.

http://www.guardian.co.uk/medicine/story/0,,1583671,00.html

And then it earned its bad reputation, but both have long half lives, Valium the longest, and thus less likely for abuse.


 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » yxibow

Posted by ed_uk on April 4, 2006, at 15:57:59

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk, posted by yxibow on April 4, 2006, at 1:15:17

Hi Yxi

>5

You said 10, I said 4. Some people say 3. I'm not sure what you're getting at here. 4 seems like a reasonable compromise between 3 and 5. It's only an approximation of course, and shouldn't be taken too seriously. It will vary from person to person anyway.

>both have long half lives, Valium the longest, and thus less likely for abuse

Diazepam and chlordiazepoxide are both metabolised to desmethyldiazepam. The likelihood of 'abuse' doesn't generally have much to do with half life, it's got more to do with whether or not a drug 'kicks in' suddenly and rapidly or not. Drugs with a rapid onset of action have greater recreational value eg. alcohol.

Ed

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk

Posted by yxibow on April 5, 2006, at 0:57:21

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » yxibow, posted by ed_uk on April 4, 2006, at 15:57:59

> Hi Yxi
>
> >5
>
> You said 10, I said 4. Some people say 3. I'm not sure what you're getting at here. 4 seems like a reasonable compromise between 3 and 5. It's only an approximation of course, and shouldn't be taken too seriously. It will vary from person to person anyway.

Exactly. Some sources have said up to 10, thats why I said 10. I corrected to 5 from the first table in the dr-bob benzo list which I see as mostly accurate from my experience with benzodiazepines.

>
> >both have long half lives, Valium the longest, and thus less likely for abuse
>
> Diazepam and chlordiazepoxide are both metabolised to desmethyldiazepam. The likelihood of 'abuse' doesn't generally have much to do with half life, it's got more to do with whether or not a drug 'kicks in' suddenly and rapidly or not. Drugs with a rapid onset of action have greater recreational value eg. alcohol.

Exactly, which is why Librium is used for alcohol abuse situations because it does not have nearly the kick and strength of Valium, which is why Valium really became the drug of choice of the brain child of Leo Sternbach.

However, Valium these days has lost its street value for the most part, this isnt the 70s -- Xanax is much higher I would bet.

And you're right about the metabolism, Librium has 4 metabolites though, that is just one of them. Valium has 3, two in common with Librium.

But that doesn't stop my belief that Ashton, or rather, the website that the person created who quotes her, is dangerous.

And being a UK site, it perhaps reflects the position of doctors in your country towards a medication class that while in some people can be habituated towards, helps millions of people around the world.

I still (yes I disclose that I take high dose Valium and thats a concern, but a possible necessity at the moment) believe that under the care of the right doctor, benzodiazepines are among the safest psychoactive drugs purely due to their very long history, over barbiturates, reducing the chance of overdosage.

As we examine drug classes closer and closer to the present, we are in a state of flux. TCAs, probably about the same, 50 years, with imipramine.

SSRIs, about 20-25 years, old line antipsychotics, 50 years, atypical antipsychotics, 40 years or so with Clozaril, around 10 years with Risperdal, and its followers.

Who knows what will be the drug of tomorrow -- but we can only estimate patient years in studies, in vitro -- in vivo of course is post marketing

Cheers

-- Jay

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please! » ed_uk

Posted by naughtypuppy on April 5, 2006, at 10:01:56

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please! » Sobriquet Style, posted by ed_uk on April 3, 2006, at 13:53:18

Actually I've got a prn presription for chlordiazepoxide and can feel the effects fairly quickly (within a couple of hours). I didn't care for using it chronically though. It caused bruxism, anorgasmia and dental pain after a while. I discontinued entirely on my own accord. A good technique for tapering is to dissolve the capsule in 100ml of water and drink half of it every day. Next week, double the amount of water, but drink the same volume and so forth. This prevents you from having to buy different strengths just to wean yourself off the med (ever notice that different stregths are about the same price? defies logic doen't it?). No discontinuence symptoms whatsoever, so at least in my mind Ashton is just a fear monger who likes the attention. I can still use benzos prn with no problems.

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please! » naughtypuppy

Posted by ed_uk on April 5, 2006, at 13:44:17

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please! » ed_uk, posted by naughtypuppy on April 5, 2006, at 10:01:56

Hi

>Actually I've got a prn presription for chlordiazepoxide and can feel the effects fairly quickly (within a couple of hours).

A couple of hours is fairly slow compared with the rapid-acting benzos like Valium and Xanax. Most people feel them start to work in less than an hour.

Kind regards

Ed

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please! » naughtypuppy

Posted by ed_uk on April 5, 2006, at 13:48:10

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please! » ed_uk, posted by naughtypuppy on April 5, 2006, at 10:01:56

>ever notice that different stregths are about the same price? defies logic doen't it?)

This is particularly true of a lot of very expensive new meds eg. 30 caps 200mg £60, 30 caps 400mg £60.

When it come to drugs like Viagra and Cialis, people can safe a lot of money if they purchase a pill splitter!

Regards

Ed

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » yxibow

Posted by ed_uk on April 5, 2006, at 13:59:41

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk, posted by yxibow on April 5, 2006, at 0:57:21

Hi Yxi

>Some sources have said up to 10, thats why I said 10

I never read that before! Most sources say 3 or 5! ......which is why I tend to say 4.

>Exactly, which is why Librium is used for alcohol abuse situations because it does not have nearly the kick and strength of Valium, which is why Valium really became the drug of choice of the brain child of Leo Sternbach.

But if someone is taking a benzo on a daily basis they don't need to feel it 'kick in'. They need a drug which provides continuous 24hr relief of anxiety. Chlordiazepoxide can fulfill this role for patients who do not require a high dose of a benzodiazepine. It doesn't really matter whether they are taking 20mg diazepam or 80mg chlordiazepoxide.

Diazepam is, as we have already noted, a better PRN than chlordiazepoxide. I wasn't recommending chlordiazepoxide as a PRN, I was simply suggesting that it was an alternative to diazepam in the treatment of chronic anxiety.

Ed

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk

Posted by yxibow on April 6, 2006, at 1:20:53

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » yxibow, posted by ed_uk on April 5, 2006, at 13:59:41


> But if someone is taking a benzo on a daily basis they don't need to feel it 'kick in'. They need a drug which provides continuous 24hr relief of anxiety.

True, you are correct -- I didn't mean the kick of Xanax, a more subtle one. I can notice differences between Valium and the previous Klonopin in terms more of anxiety relief. Maybe its the placebo syndrome, but if so, so what. And it does provide continuous 24 hour relief, past 24 hours actually though I take it twice daily because I took Klonopin twice daily too and the extra curve of onset at different times of the day helps, in my opinion. But that's just my case. Others will obviously vary tremendously since I have a special syndrome :/.


Chlordiazepoxide can fulfill this role for patients who do not require a high dose of a benzodiazepine. It doesn't really matter whether they are taking 20mg diazepam or 80mg chlordiazepoxide.


Mostly.... metabolites of diazepam are a little stronger I think, since Restoril is among them, I think it is not among Librium -- but no need to quibble. :)

>
> Diazepam is, as we have already noted, a better PRN than chlordiazepoxide. I wasn't recommending chlordiazepoxide as a PRN, I was simply suggesting that it was an alternative to diazepam in the treatment of chronic anxiety.

mmph... I would say Xanax or Ativan provides better PRN relief for onset time. Librium really is a fading drug, certainly here in the US I think except for some esoteric alcohol abuse reduction.

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » yxibow

Posted by ed_uk on April 6, 2006, at 14:42:00

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk, posted by yxibow on April 6, 2006, at 1:20:53

Hi Yxi

>I would say Xanax or Ativan provides better PRN relief for onset time.

I find that diazepam works more quickly than lorazepam.

>Librium really is a fading drug, certainly here in the US I think except for some esoteric alcohol abuse reduction.

Diazepam is a fading drug in the US too, but that does not mean that it's valueless!

Regards

Ed

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk

Posted by Phillipa on April 6, 2006, at 19:03:50

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » yxibow, posted by ed_uk on April 6, 2006, at 14:42:00

Personal experience is the best indicator to me. I've taken them all at some point in my life. And valium definitely worked better taken three times a day although I take only twice a day now. And it doesn't provide relief for a panic attack sorry it just doesn't. But take a xanax and within l5minutes you feel the calming effects and I always took it up to 4-5 times a day for years by prescription. And klonopin nothing but depression . And librium even in the beginning didn't begin to touch anxiety. The very best if you want sleep too is chloral hydrate old but works for babies and elderly and is safe. just don't drink on it. And if you really want to stop a panic attack dead in it's tracks drink around 3-4 beers. In my opinion after over 30years the best antianxiety med is booze. And the l0 years I've wasted on AD's would have been saved had I continued drinking. But no the pharmacitical companies need to make money . So now everything is addictive so atypical antipsycotics. Back to alchohol first for me. I'd rather have l0 quality years of life then l0 year of +ell. Love Phillipa ps and they are not hard to get off of I've done it on my own more than once cause as your anxiety goes down you just don't need as high a dose of a benzo.And I forgot how the thread started just my rant for the day.

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please! » ed_uk

Posted by Sobriquet Style on April 7, 2006, at 8:04:17

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please! » Sobriquet Style, posted by ed_uk on April 3, 2006, at 13:53:18

>Have you ever tried chlordiazepoxide (Librium)?

No...

>Chlordiazepoxide is easier to taper than most benzos (similar to diazepam).

Thats seems a very good advantage.

>and so your doc may be more comfortable prescribing it.

Thats good to know. :-)

>Chlordiazepoxide is not a good PRN benzo, it doesn't 'kick in' as quickly as Xanax or Valium. It is, however, a logical choice if a benzo is to be taken daily for several weeks or more.

In some respects I think I could benefit from chlordiazepoxide. I think though, because I really want to avoid using a benzo daily, my first choice is diazepam, more so because of the PRN advantage and together with the long half-life, i'm hoping i'll only need to take it 2-3 days a week max. Guess I won't know till I try, but if valium doesn't work out too well, perhaps Librium when be my next choice. I really want to stay with as low dosage and weakest benzo's at all costs. I think my anxiety although servere at times, is mild other times, so just to fade out the unpleasent anxiety when needed will be a god send.

Thanks for the info :-)

~

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » Phillipa

Posted by ed_uk on April 7, 2006, at 17:05:49

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk, posted by Phillipa on April 6, 2006, at 19:03:50

>And valium definitely worked better taken three times a day although I take only twice a day now.

Librium would probably have worked just as well if you took an adequate dose. You'd need about 80mg Librium to substitute for 20mg diazepam. I doubt you were prescribed 80mg. 10mg three times a day is a common dose, but it's probably not enough.

>And it doesn't provide relief for a panic attack sorry it just doesn't.

Valium normally kicks in just as fast as Xanax. Don't forget than Xaxax is much more potent than Valium. 4mg Xanax is approximately equivalent to 40-80mg Valium. Not many people take 80mg Valium. I maintain than Valium can be effective for panic attacks.

Ed


 

Diazepam in panic disorder

Posted by ed_uk on April 7, 2006, at 17:35:37

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk, posted by Phillipa on April 6, 2006, at 19:03:50

J Clin Psychiatry. 1996 Aug;57(8):349-55.

Diazepam versus alprazolam for the treatment of panic disorder.

Noyes R Jr, Burrows GD, Reich JH, Judd FK, Garvey MJ, Norman TR, Cook BL, Marriott P.

Department of Psychiatry, University of Iowa, College of Medicine, Iowa City 52242-1000, USA.

BACKGROUND: Alprazolam has proven efficacy as a treatment for panic disorder, but the place of other benzodiazepines is less well established. METHOD: To compare the efficacy and tolerability of diazepam and alprazolam for the disorder, a placebo-controlled, double-blind trial was undertaken in two sites. Two hundred forty-one subjects with panic disorder or agoraphobia with panic attacks were randomly assigned to flexible doses of diazepam, alprazolam, or placebo for 8 weeks. RESULTS: At the end of the trial, over 60% of subjects taking either diazepam or alprazolam were at least moderately improved compared with less than 30% of those taking placebo. On all measures of efficacy, subjects taking diazepam and alprazolam showed an equally favorable response. Despite some sedation early in the trial, both drugs were tolerated well. More severely ill subjects responded less well to either benzodiazepine. CONCLUSION: The results indicate that diazepam is an effective alternative to alprazolam for the treatment of panic disorder.

 

Re: Diazepam in panic disorder » ed_uk

Posted by tizza on April 9, 2006, at 4:22:09

In reply to Diazepam in panic disorder, posted by ed_uk on April 7, 2006, at 17:35:37

hey Ed hows it going? I agree with you about xanax v's valium in it's effective properties for anxiety. I would choose valium anyday over xanax. You just need to give valium a go, it doesn't work as fast as xanax but it works way better in long term treatment for anxiety disorders than xanax ever will. Well it does for me anyway. Paul

 

Re: Diazepam in panic disorder » tizza

Posted by ed_uk on April 9, 2006, at 12:39:01

In reply to Re: Diazepam in panic disorder » ed_uk, posted by tizza on April 9, 2006, at 4:22:09

Hi T!

Things are going ok in general :) ....but I just wasted most of the day in bed. Sunday is the only day when I don't work so I tend to sleep a lot on Sundays. I always feel bad if I don't get up all day. I feel like such a waster. I finally got out of bed at 6pm. I'm tired on Sunday's sure but I need to stop wasting the whole day. It's counterproductive because my night time sleep ends up disturbed and I feel worse on Monday as a result.

How are you doing?

>it doesn't work as fast as xanax

They both take about an hour to 'kick in' for me. The dose of Valium needs to be a lot higher to get the same relief. Valium is a good PRN provided that the dose is adequate - I always needed at least 10mg, usually more.

Kind regards

Ed

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please

Posted by boveni3 on August 5, 2007, at 22:14:29

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » ed_uk, posted by yxibow on April 5, 2006, at 0:57:21

I found your logic alarming and am greatly concerned for your well-being.


"yes I disclose that I take high dose Valium and thats a concern, but a "possible" necessity at the moment"

Of course you justify benzos. Possible necessity; don't you think you should be sure!

"I still believe that under the care of the right doctor, benzodiazepines are among the safest psychoactive drugs purely due to their very long history, over barbiturates, reducing the chance of overdosage."

If your boat is sinking slower than another, does that mean you're doing better?

You're addicted to a drug, but less likely to overdose, so that's ok?

I maintain my concern for you well-being and only wish you well.

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » boveni3

Posted by Phillipa on August 5, 2007, at 22:30:14

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please, posted by boveni3 on August 5, 2007, at 22:14:29

My pdoc never even heard of her. After 35years of benzos not stopping even though I've developed some tolerance I don't raise the dose. Love Phillipa

 

Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » Phillipa

Posted by Squiggles on August 9, 2007, at 15:13:52

In reply to Re: Someone Prove Ashton Wrong!!!!!!!!!!....Please » boveni3, posted by Phillipa on August 5, 2007, at 22:30:14

> My pdoc never even heard of her. After 35years of benzos not stopping even though I've developed some tolerance I don't raise the dose. Love Phillipa

They're starting to catch on though; Health Canada and the FDA have reaassessed the Schedule for benzos on their addicitive capacity.

Also, clonazepam can be taken for a long time without great tolerance, while others cannot.

Dr. Ashton is a specialist in the area. The fact that she has not been consulted 20 yrs. ago, does not mean that benzo addiction had not done considerable damage.

There is a great change now even in the pharma blurbs.

Squiggles

 

Re: Tolerance to Benzo Anxiety Effects

Posted by FredPotter on August 9, 2007, at 15:52:08

In reply to Tolerance to Benzo Anxiety Effects, posted by Sobriquet Style on March 30, 2006, at 7:28:25

I'm not sure how withdrawal symptoms appear even in the presence of the drug. Is this another way of saying tolerance and needing a progressively higher dose?

 

Re: Tolerance to Benzo Anxiety Effects » FredPotter

Posted by Squiggles on August 9, 2007, at 16:05:45

In reply to Re: Tolerance to Benzo Anxiety Effects, posted by FredPotter on August 9, 2007, at 15:52:08

> I'm not sure how withdrawal symptoms appear even in the presence of the drug. Is this another way of saying tolerance and needing a progressively higher dose?

Tolerance means that a higher dose than the initial one given for condition x, becomes necessary with time. Time varies according to type of benzo (with its half-life), length of time taken, and amount.

Withdrawals from the above conditions, will also vary, but are more like a corrollary to that and not the same as tolerance. So, you can have withdrawals of a different type and severity even with a small dose of say Xanax after 3 months.

Squiggles

 

Re: Tolerance to Benzo Anxiety Effects » Squiggles

Posted by Phillipa on August 9, 2007, at 21:50:05

In reply to Re: Tolerance to Benzo Anxiety Effects » FredPotter, posted by Squiggles on August 9, 2007, at 16:05:45

Squiggles going on 40 years and I take less than in the beginning. Love Phillipa ps we're all different

 

Re: Tolerance to Benzo Anxiety Effects » FredPotter

Posted by Quintal on August 10, 2007, at 3:50:53

In reply to Re: Tolerance to Benzo Anxiety Effects, posted by FredPotter on August 9, 2007, at 15:52:08

>I'm not sure how withdrawal symptoms appear even in the presence of the drug. Is this another way of saying tolerance and needing a progressively higher dose?

This is an interesting explanation:
__________________________________________________

A study into the effects of the benzodiazepine receptor antagonist, flumazenil, on benzodiazepine withdrawal symptoms persisting after withdrawal was carried out by Lader and Morton.[5] Study subjects had been benzodiazepine free for between 1 month and 5 years but all reported persisting withdrawal effects to varying degrees. Persistent symptoms included clouded thinking, tiredness, muscular symptoms such as neck tension, cramps and shaking and the characteristic perceptual symptoms of benzodiazepine withdrawal, namely, pins and needles, burning skin, pain and subjective sensations of bodily distortion. Therapy with 0.2-2mg of flumazenil intravenously was found to decrease these symptoms in a placebo controlled study. This is of interest as benzodiazepine receptor antagonists are neutral and have no clinical effects. The author of the study suggested that the most likely explanation is that past benzodiazepine use and subsequent tolerance had locked the conformation of the GABA-BZD receptor complex into an inverse agonist conformation and that the antagonist flumazenil resets benzodiazepine receptors to their original sensitivity.
http://en.wikipedia.org/wiki/Benzodiazepine_withdrawal_syndrome
--------------------------------------------------

Although the underlying mechanisms of benzodiazepine dependence are still not entirely understood, research in animals points to the clinical potential for the benzodiazepine antagonist flumazenil (Ro 15-1788) to reverse benzodiazepine dependence and tolerance and prevent withdrawal (Whitwam, 1988). Administration of flumazenil reverses tolerance and dependence to benzodiazepines (Gonsalves and Gallager, 1985) but precipitates recognizable withdrawal symptoms . However, if given during chronic treatment flumazenil can, by similarly reversing tolerance, prevent subsequent withdrawal syndromes in primates (Gallager, Heninger and Heninger, 1986) and in rats (Baldwin, Hitchcott and File, 1990). One explanation for this is the antagonism and depletion of an endogenous benzodiazepine receptor ligand with inverse agonist and thus anxiogenic activity by the antagonist flumazenil (Baldwin, Hitchcott and File, 1990). However, levels of the proposed 'anxiety peptide' ligand associated with diazepam binding inhibitor (DBI) were not found to be increased by the administration of diazepam in rats (Ball et al., 1987). An alternative explanation is that chronic agonist use causes a persistent conformational change and thus a shift in benzodiazepine receptor efficacy in the direction of inverse agonist function (Little, Nutt and Taylor, 1987) and that flumazenil resets the receptor's sensitivity (Nutt and Costello, 1988). In binding to the benzodiazepine receptor flumazenil may alter the coupling of the elements of the GABA/benzodiazepine macromolecular complex modified by benzodiazepine binding, thus restoring the GABA recognition site to its pre-drug affinity (Gonsalves and Gallager, 1985).
http://www.bcnc.org.uk/flumazenil.html
__________________________________________________

Q


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