Talk:Clonazepam

From Wikipedia, the free encyclopedia

As usual on talk pages, please start new threads at the bottom of the page.

	Clonazepam is part of WikiProject Pharmacology, a project to improve all Pharmacology-related articles. If you would like to help improve this and other pharmacology articles, please join the project. All interested editors are welcome.
B	This article has been rated as B-Class on the quality scale.
Mid	This article has been rated as Mid-importance for this Project's importance scale.

[edit] Image permission (2004)

The image of the chemical structure of Clonazepam was taken from http://www.biopsychiatry.com/clonazepam/clonazepam.jpg

I e-mailed the owner of biopsychiatry.com at info@bltc.com and asked permission to use his images and content on Wikipedia.

He replied thus:

David Pearce wrote:

> At 20:03 08/06/2004, you wrote:

>> What is your policy on allowing images and text from your HedWeb site to be used on Wikipedia?

> Hi Mike

> You're welcome to use anything of interest

> The Wikipedia is a fantastic project!

> very best wishes from sunny Brighton

> Dave

[edit] Tobacco concomitantly

Pardon the intrusion. However I am a college student in New York studying chemistry and pharmacology and was wondering if anyone could inform me as to what mechanism of action tobacco's role plays in decreasing the effects of Clonezapam (Klonopin), and Diazepam (Valium). Username: a1970sweet If anyone has any information regarding this matter I would greatly appreciate it and if you could simply post it under my paragraph here. Thank-you.

[edit] Problems with References

I tried to clean up some of the inline references such that they show up in the reference heading, but met with very limited success. The reference numbers did start showing up inline, but the full citations aren't appearing.

Some of the references, given only as hyperlinks, seem questionable and should be verified by someone with access to full text Howard C. Berkowitz 21:16, 6 July 2007 (UTC)

[edit] Hapten

Would someone clarify? There is an immunological response to Clonazepam?

[edit] Dosage equivalents and pharmacology

It should be noted that different benzodiazepines, different people, etc. react differently. I find it hard to believe, based on personal use, that 10 mg diazepam = 0.5 mg Clonazepam, diazepam being "stronger". Is it not true that Clonazepam does not activate as many receptors as Diazepam?

diazepam walks the line where benzo's meet.... something... lol.... and clonazepam has a more spread out less noticable effect than valium. i take clonazepam .5mg 3x a day —Preceding unsigned comment added by 76.170.119.175 (talk) 14:00, 26 November 2007 (UTC)

[edit] Safe taking with Sleep Apnea?

Is Clonazepam meant to be taken in the morning after breakfast and/or as a sleep/anxiety aid just before bedtime?

Response: I don't know if it is safe with sleep apnea, but regarding when it is meant to be taken...it depends upon the specific situation of the patient and judgment of the prescribing physician. Anxiety sufferers may take Clonazepam at any time during the day as an "as needed" medication or as a maintenance treatment. For others, it is used as a sleep aid. For example, some anti-depressants are engergizing (Effexor for example) which make it difficult for those taking it to sleep. Low doses of Clonazepam may be prescribed in that situation to be taken in the evening. Tobycat 03:36, 20 Apr 2005 (UTC)

I was diagnosed as a Textbook "REM Sleep disorder", In which I talk, move, and walk during sleep. My Sleep clinic doctor prescribed me 5mg Clonazepam before bedtime, then doubled the dose to 10mg when that didn't do anything for me. Qexter 08:36, 8 Jun 2006 (EST)

5 mg of clonazepam is a huge dose to take all at once; 10 mg - taken as a single dose - is practically an anesthetic. Either you were taking DIazepam (Valium), for which these would be normal doses, or you left out a couple of decimal points. Did you mean 0.5 mg and 1.0 mg, Qexter? If not, and you really were taking these high doses of Klono, you must have been very sleepy the next day. 68.83.140.156 04:56, 24 August 2006 (UTC)Essex9999

I have obstructive sleep apnea (for 16 years now with CPAP) and have been taking 2 mg of Clonazepam about 1 hr before I want to pass out. I awake either six hours later if my bladder is full and go back for my REM sleep (which for me is after six hours of sleep usualy) or usually sleep eight to nine hours. I feel great when I wake up.

[edit] What is the dose of Clonazepam conpared to Valium and Xanax?

What is normal dose for medical, and recreational use of clonazepam?

Recreational use of clonazapam? Go away. JFW | T@lk 07:50, 17 July 2005 (UTC)

That was a very rude comment from someone who indulges in the recreational use of drugs such as alcohol and coffee, according to his user page. Stanfordandson 01:07, 22 June 2006 (UTC)

Hey, this is useful (potentially life-saving) information (recreational doses are generally well within the range of medicinal doses). In general:

Diazepam (Valium) 10mg

Alprazolam (Xanax) 0.5mg

Clonazepam (Klonopin) 0.5mg

Lorazepam (Ativan) 1.0mg

Temazepam (Restoril) 20mg

http://www.benzo.org.uk/bzequiv.htm

A starter dose is typically somewhat below that benchmark (0.5mg Ativan, for example) but the above are all generally equivalent and is a usual dose for a benzodiazepine. The dose builds with tolerance (I know somebody who takes 4mg Klonopin daily for maintenance, which comes out to dosing (in theory) eight times a day). Benzos aren't very fun in general unless you need them and can be very nasty indeed. A word to the wise.

[edit] Heart beats and Clonazepam

A daily, small dose of Clonazepam (0.5mg or less) can cause high heart beats? Like 130-150 in a "normal" state, not doing exercise or heavy physical activity.

Response: seems unlikely. I was having some mild panic attacks, with symptoms including a racing heart, and was prescribed low dose Clonazepam for as-needed treatment.

unless your having a very rare side effect and getting panic attacks from an axiety med... than if say your either mixing it with something... you smoke ciggerettes...drink alot of coffee... or your alergic

(anything that stimulates the CNS like nicotine or caffeine metabolizes the klonopin alot faster than normal which can cause panic attacks... but the mostly likly cause of tachycardia after taking a benzo is an allergy or an unlucky adverse reaction) —Preceding unsigned comment added by 76.170.119.175 (talk) 14:05, 26 November 2007 (UTC)

[edit] Indication vs. Approval

Regarding Davidruben's revert to the indications section (http://en.wikipedia.org/w/index.php?title=Clonazepam&diff=prev&oldid=74429734): Look at the sentence on Tourette Syndrome. It's clearly confusing FDA approval with the more general concept of a commonly-accepted use. And what's the point of even mentioning that something is an off-label use (which is, after all, a US-specific regulatory issue) in a general article on the substance? I can see it in the case of Vioxx, but not here. KonradG 00:53, 8 September 2006 (UTC)

I agree in part. "Off-label" use probably exceeds FDA approved use for many drugs, even if we limit our discussion to the United States. Even before FDA approval as an anxiolytic in the late 90s, Klonopin was far more often prescribed for anxiety than the relatively few and exotic convulsive disorders for which it was officially approved in 1975. Having said that, simply denoting which indications are FDA sanctioned is useful for a potential consumer. Many off label uses rely exclusively on anecdotal evidence JE1977 02:30, 4 March 2007 (UTC)

I find that's very rarely the case. Can you name a single example? A drug's indication represents the mainstream view of the medical community. Any claim that a particular indication is not backed by evidence is therefore not a mainstream view, and as such needs to have solid references. The fact that a particular use is off-label doesn't tell you anything by itself. And in almost all cases will mislead the average consumer because "approval" is such a vague word. KonradG 03:54, 6 March 2007 (UTC)

Indications for a particular drug vary by which text one consults. My fault, when I say anecdotal evidence I mean clinical experience (i.e. no scientific studies exist or only low quality studies exist to recommend a drug for a particular purpose) Case in point: the practice of prescribing Dexedrine to augment Nardil. Conventional wisdom says this is huge no no, but experienced psychiatrists do just this albeit with strict blood pressure monitoring. Prescribing opiates as a last ditch attempt to alleviate treatment resistant severe depression is another. Many doctors will not deviate from the indications on the label for fear of legal liability (especially true concerning scheduled drugs) and some insurance companies will not pay for "off label" prescriptions. So it is useful for consumers to know the FDA labeled indications. Plus listing the FDA labeled indications is standard on pretty much all drug monographs printed in America. JE1977 02:46, 7 March 2007 (UTC)

Monographs contain that info because they're legally required to. Encyclopedias aren't, and therefore they're free to get medical information from doctors instead of lawyers. Anyway, what you're talking about are experimental treatments, not indications. There's no reason to mention that an indication is off-label, especially when you don't even know if the reader is from the US. As for a doctor's legal liability, that isn't affected by FDA approval, except as far as it provides evidence that the use was a medically accepted one. The FDA doesn't regulate medical practice. KonradG 17:16, 7 March 2007 (UTC)

[edit] Clonazepam Hangover

I am a long-term user of Clonazepam for generalized anxiety disorder since I was 17 and I and others who have taken my medication have noticed a distinct "Clonazepam Hangover" effect. When you take it before you go to bed, you wake up feeling many similar symptoms of an alcohol hangover such as dizziness, irritability, drowsiness, and a headache. This is probably due to the half-life of the medication in your system as well as the way it interacts with your brain while you sleep, as benzos in general have a tendency to interfere with REM sleep. If you don't mind I would like to add a small segment containing some information about such, as I am a long-term user. I will not couch it in absolute language but instead say "Some users complain of "hangover like" symptoms." or something like that. —The preceding unsigned comment was added by Bbcrackmonkey (talk • contribs) 12:02, 13 February 2007 (UTC).

"I suggest taking it upon waking only. If you have insomnia, there are numerous other substances that are less addictive. If you are treating anxiety, klonopin PO AC 1x/day" —Preceding unsigned comment added by 76.121.93.138 (talk) 20:09, 14 February 2008 (UTC)

Go for it, but make sure it's verifiable from somewhere other than your own experience. That generally means the information has to have been published somewhere in a reliable source. KonradG 12:16, 13 February 2007 (UTC)

I would speculate that the hangover has nothing to do with REM sleep and everything to do with the long half life. Most antidepressants suppress REM sleep, suppressing REM sleep in and of itself has a mild antidepressant effect (although this is neither necessary nor sufficient to treat depression), and the increased REM-sleep during withdrawal of benzodiazepine hypnotics is often described as unpleasant. The purpose of the various stages of sleep is unknown, but most people do not miss their REM sleep if it is taken away. I suspect the long half life is to blame for the hangover.

I once heard a barbiturate hangover described as being "half high. You are not high enough to enjoy it, but enough drug remains to be bothersome and cause side effects." However, I get the feeling that Bbcrackmonkey is not talking about the same thing. Bbcrackmonkey, would you get a hangover by the evening if you had taken clonazepam in the morning? Is the timing during the day important?66.92.68.214 (talk) 15:00, 23 May 2008 (UTC)

It appears that the publicists at Roche Pharmacy keep editing this entry to downplay clonazepam's negative effects. We'll see what tune they sing when the class-action lawsuit against mis-prescribing of long-term clonazepam rolls around. There is no scientific evidence that benzodiazapines effectiviely treat insomnia or anxiety long-term. Shades of Upjohn, anyone? —Preceding unsigned comment added by 204.14.61.157 (talk • contribs) 21:53, 5 July 2007 (UTC) (comment moved from body of article by Precious Roy 11:36, 6 July 2007 (UTC))

I have never worked for a pharmaceutical company, although I have been involved in pharmacological research, especially in expert systems for prescribing (i.e., I'm not a doctor but I play one on computers), and worked with medical school psychopharmacologists. Expert system rule bases do contain off-label indications, with appropriate cautions. Over the last few days, I have deleted anonymous opinions on clonazepam, which are in the form of attacks (as the above talk comment moved from the article page, accusing Roche publicists and making dark threats about class action).

My concern is the apparent non-neutral point of view posts and edits regarding the long-term use of benzodiazepines in the range of anxiety disorders, including panic and social anxiety disorder. The short-term role of benzodiazepines is clear in these areas, but there are fewer studies of long-term effects: http://www.medscape.com/viewprogram/2997_pnt "Highlights of the International Congress of Biological Psychiatry [2004], Treatment of Anxiety Disorders: An Update", Pollock R and Kuo K.

I do not argue that the core drugs for long-term treatment of panic disorder, social anxiety disorder, and generalized anxiety disorder are SSRIs (especially atypical ones) and anticonvulsants, as well as desensitization therapies such as CBT and EMDR. Benzodiazepines have a fairly clear short-term role. I see the issue as the role of benzodiazepines, especially clonazepam, in long-term treatment of patients resistant to the core drugs. From the Medscape survey, where the review authors cite Fisher PL, Durham RC. Psychol Med. 1999 Nov;29(6):1425-34 "Recovery rates in generalized anxiety disorder following psychological therapy: an analysis of clinically significant change in the STAI-T across outcome studies since 1990."

From the cited review, "Fisher and Durham[64] conducted a reanalysis of 6 randomized, controlled trials of psychological therapy with GAD. Individual CBT and applied relaxation, focusing on excessive worry and physiological arousal, performed well, with overall recovery rates of 50% to 60% at 6-month follow-up. In general, GAD patients are responsive to treatment; however, they are also sensitive to medication side effects. Combined pharmacotherapy (eg, benzodiazepines plus SSRIs) or pharmacotherapy plus CBT may be appropriate for treatment-resistant patients" I see combined therapy as a legitimate off-label use in carefully selected patients.

I suggest that this article be locked against anonymous updates. Howard C. Berkowitz 13:29, 6 July 2007 (UTC)

You may request that at WP:RFPP. Fvasconcellos (t·c) 21:25, 6 July 2007 (UTC)

[edit] Dosage forms

The article says "liquid solution (2.5mg per ml) and for injection (1mg per ml)". Those seem really high (usually dosages for oral liquids are in teaspoons or 5 mL). Searching Google for "clonazepam oral solution" (what "liquid solution" presumably means) I come up with 1 mg/5 mL and 0.5 mg/5 mL, which seem more likely... It originally said "liquid concentrate" and "injection concentrate" (see this diff). Does that mean those are intended to be diluted? I work in retail pharmacy so I'm not familiar with these things... --Galaxiaad 03:12, 5 August 2007 (UTC)

No, this solution are oral drops. 1mL = 25 drops = 2.5 mg. 1 drop = 0.1 mg clonazepam. Are oral drops uncommon in the US?--84.163.97.230 20:30, 4 November 2007 (UTC)

Oh... I'm only familiar with infants' drops, but thanks for pointing out what this was referring to--makes a lot more sense now. --Galaxiaad (talk) 03:33, 25 February 2008 (UTC)

[edit] Long-term brain damage

There is a dispute here that will not be solved in the main page. Under the circumstances, if there is a question what a cited source actually said, it would be appropriate fair use to include the conclusions as a direct quote.

"Protracted withdrawal results from structural brain damage, which is often irreversible.[14]"

This was challenged (not sure by whom):

Ashton never stated this, Do benzodiazepines cause structural brain damage? These results have raised the question of whether benzodiazepines can cause structural brain damage. Like alcohol, benzodiazepines are fat soluble and are taken up by the fat-containing (lipid) membranes of brain cells. It has been suggested that their use over many years could cause physical changes such as shrinkage of the cerebral cortex, as has been shown in chronic alcoholics, and that such changes may be only partially reversible after withdrawal. However, despite several computed tomography (CT) scan studies^{[citation needed]}, no signs of brain atrophy have been conclusively demonstrated in therapeutic dose users, and even the results in high dose abusers are inconclusive. It is possible that benzodiazepines can cause subtle changes which are not detected by present methods, but on the available evidence there is no reason to think that any such changes would be permanent.

Howard C. Berkowitz 03:34, 6 September 2007 (UTC)

Prof Ashton has said that benzodiazepines may cause structural brain damage in the peer reviewed medical literature. She said so in this publication [[1]] --Kazlow101 19:01, 16 September 2007 (UTC)

I agree that she alludes to the possibility in the abstract: "The protracted nature of some of these symptoms raises the possibility that benzodiazepines can give rise not only to slowly reversible functional changes in the central nervous system, but may also occasionally cause structural neuronal damage." It's hard to assess the probabiity just from the abstract. My sense is that your "may cause structural brain damage" is a little stronger than what I'd infer from the language of such an abstract. If you have access to the original article and it gives probabilities, odds ratios, counts of observed damage, etc. by all means cite them. If it's only an opinion stated in the main article, that is worthy of mention, but from the abstract, I can't tell whic it is. An abstract such as pubmed is for finding the article in order to assess its content. An abstract doesn't quite, to me, equate to "peer-reviewed medical literature." Howard C. Berkowitz 19:30, 16 September 2007 (UTC)

any inorganic material that enters the bloodstream... goes to your brain... and screws with the way it works probably isnt too great for ya in the long run.... logic mabye —Preceding unsigned comment added by 76.170.119.175 (talk) 14:07, 26 November 2007 (UTC)

I did a whole reedit of the protracted withdrawal section and reworded it so that it is no longer taking out of context what prof ashton said in her published papers. There is also a citation which disputes protracted withdrawal, so I think that the section is sorted out now.--Stilldoggy (talk) 00:55, 25 March 2008 (UTC)

[edit] klonopin withdrawal

Someone should add a section to the article about people who have gotten addicted to benzos from long term theraputic use. These drugs can have as bad effects as heroin for some long term users and most people know nothing about this. It would be a favor to consumers for a knowledgeable party which is not affiliated with the drug industrial machine to write something on this. —Preceding unsigned comment added by 146.113.65.31 (talk) 17:45, 11 January 2008 (UTC)

I just got out of a detox center for abusing klonopin and ritalin. I have been given phenobarbitol to "bring me down" from the Klonopin. This seems to not be working, I'm suffering severe free floating panic and anxiety attacks, constant hot/cold, vivid awful nightmares, insomnia, generally awful. Does anyone know if the phenobarb is gonna help or is this just something I have to go thru? Thanks for any info. —Preceding unsigned comment added by 76.106.74.22 (talk) 22:26, 10 November 2007 (UTC)

Obviously, I can't give you diagnostic and treatment information in this medium; it's something you will have to discuss with your treating physician. With all those caveats, clonidine, possibly in patch form, may help with such symptoms. Howard C. Berkowitz 23:59, 10 November 2007 (UTC)

sounds like withdrawel. the phenobarbitol will help ease some of the symptoms but the best way to get through wothdrawels is to simple get through em,

oh and the phenobarbitol may have some mild withdrawels of its own seeing as its a barbituate. but if u use it for the other withdrawel and then wean yourself off the barb u should have to suffer as much —Preceding unsigned comment added by 76.170.119.175 (talk) 14:10, 26 November 2007 (UTC)

[edit] Chemical name discrepancy?

The lede currently says "[…] Clonazepam, also known as 5-(2-chlorphenyl)-1, 3-dihydro-7-nitro-2H-1,4benzodiazepin-2-one, is […]".
The Drugbox currently says "[…] IUPAC_name = 6-(2-chlorophenyl)-9-nitro-
2,5-diazabicyclo[5.4.0]undeca-
5,8,10,12-tetraen-3-one […]".

They are pretty different. Is one wrong? I don't remember enough chemistry to be able to tell. — ¾-10 19:44, 12 December 2007 (UTC)

None of them is wrong; the IUPAC name is the fully systematic one (the ...2,5-diazabicyclo[5.4.0]undeca-tetraene), whilst the older less-systematical name is that of a 2H-benzo-1,4-diazepine-2-one... If you'd like to put it that way, the "benzodiazepine" name is somewhat "old-stylish", but not really incorrect, and is still being widely used, mainly in pharmacology and sciences apart organic chemistry, because it stresses the benzodiazepine structure, which is a sort of key for a non-chemist to recognize the substance from this name.--84.163.92.86 (talk) 17:30, 6 January 2008 (UTC)

Also, I would plead for letting both of these names in the article, to be able to find it through search, for example.--84.163.92.86 (talk) 18:00, 6 January 2008 (UTC)

I agree completely. Thanks for explaining why they are different. Even as a chemistry-rusty person, I can follow the basic idea that the nomenclature depends on how you view the groups of components. Many thanks. — ¾-10 18:15, 6 January 2008 (UTC)

[edit] Amphetamine withdrawal

I have no doubt it is the case that Klonopin is used for this purpose, still there needs to be some way to verify the claim. This article is still in need of a lot of sources. --jenlight (talk) 05:24, 5 January 2008 (UTC)

Quite few medications are used in management of amphetamine overdose/toxicity; if all other principial (beta-blockers, antiarrhytmics, a benzodiazepine (which well could be clonazepam, e.g.), a suitable antipsychotic, electrolytes, and say, dantrolene) are mentioned as well in their articles, I'd say it's fine, maybe with an "off-label"-remark...--84.163.92.86 (talk) 17:34, 6 January 2008 (UTC)

[edit] Availability as Liquid and Injection

I'm virtually certain that this drug is not available in either liquid or injectable forms in the US as the article states. A search of my DFC resources as well as the FDA website yield no results for either. I'll wait to see if anyone has any objections, but if not I'll remove that info. Editortothemasses (talk) 20:27, 14 January 2008 (UTC)

As this is an english wiki project, you would need to check all english speaking countries before removing from the article that it is avaiable in injectable form. You would need to look at Australia, Canada, UK, south africa etc and see if they have injectable clonazepam. This abstract says that clonazepam is available in injection form.[2]

--Literaturegeek (talk) 14:36, 15 January 2008 (UTC)

Well, I don't want to be argumentative, but that abstract is from 1982. 26 years ago, it may have been made in an injectable form. I cannot find a single reference, however, to indicate that it has been made in either a liquid or injectable form in several years. Also, I realize that this is an English project, but if you read the article, it says "Clonazepam is available in the U.S. as tablets (0.5, 1.0, and 2 mg), orally disintegrating tablets (wafers) (0.125, 0.25, 0.5, 1.0, and 2 mg), liquid solutions (2.5 mg/mL) and for injection (1 mg/mL)". Therefore, since I can find no information in any of the comprehensive clinical or FDA references to suggest that it is or has been available in the U.S. (key word being U.S.) in liquid or injectable forms, my concern remains. I am not trying to be nitpicky -- I used this page as a resource that the drug was available in a liquid form when making a comment to a patient and it appears that I was wrong. Let me know what you think. Editortothemasses (talk) 18:38, 15 January 2008 (UTC)

Clonazepam is available in australia as an injection.[3],[4],[5]. The opening paragraph says about its availability in europe, canada and australia. The opening paragraph already says in what formulations clonazepam is available in , in the U.S. so american readers should be able to see that it is not available in injection form in the U.S. I don't understand what you mean by keyword U.S.--Literaturegeek (talk) 17:41, 17 January 2008 (UTC)

Oh I just reread the clonazepam wiki article. What needs to be done, is that the availability section needs to be improved to state in what formulations clonazepam is available in, in the U.S. Perhaps you could do that. This is the section that I am talking about that needs improving [6].--Literaturegeek (talk) 17:44, 17 January 2008 (UTC)

While certainly the primary scope of this article should be the anglosaxon/anglophone world (US, UK, Canada, Aus, NZ etc.), you should also keep in mind that Wikipedia (even, or better said, particularly en.wiki) is a world-wide project. I can assure you for my part, that e.g. in most (if not all) european countries, clonazepam is available as oral solution and injections; not only is it available, it is of high clinical importance. So, though I agree that an thorough edit is well in place here, to deny or "preventively-delete" this information would be wrong.--84.163.88.125 (talk) 19:08, 26 January 2008 (UTC)

Well said. I appreciate you fixing that. Editortothemasses (talk) 03:23, 27 January 2008 (UTC)

[edit] Cluttering

Stilldoggy: Please stop cluttering the benzodiazepines with a collection of refs to arbitrary pubmed articles. Those are largely reports of some experiments, which have been carried out sometime, somewhere and for some reason on rats, mice and brain slices. For almost every such article you will find a match which comes to contrary conclusions. Please limit the contribution to agreed conclusions, as found in pharmacology books and the FDA profiles, avoid anecdotal reports, speculative results, could have, may be involved, has one time been observed, is suspected, is being investigated, could have a theoretical connection etc. Not everything which has sometimes been suspected, investigated, speculated or observed is relevant to pharmacology and should be included. Avoid bot-like inclusion of search results. pubmed is not a source but an Augias-Stable of unfinished research and a playground for students. Example: You conclude that chlordiazepoxide "is related" to quinazolines, by being investigated together with quinazolines in one citation. You conclude that it is a hapten, by being mentioned in an article about immuno assay tests. These are not relevant articles for pharmacology. Of course it is a hapten in an immuno assay test! That is how antibody based immuno assays work! You develop an antibody that binds to the substance, e.g. in an urine test strip. Every substance is the hapten in an immuno assay test for this substance. But this has nothing to do with its pharmacology. Please limit yourself to agreed facts, like the FDA profiles. And the intention was NOT vandalism, but to arrive at something which looks more like the FDA fact sheet. Example: You claim as a peer reviewed fact the HIGH abuse liability of Chlordiazepoxide, because it is mentioned in a drug abuse article. FDA says low-to-medium abuse liability, placement in Schedule IV. Your edits for this page follow the same pattern. This article should end up as something like the FDA fact sheet, or a chapter from a pharmacology book, not as a collection of excerpts from arbitrary, unrelated and misunderstood pubmed abstracts, presented as "peer reviewed facts", just because they are from peer reviewed journals. This doesn't make them facts. 70.137.178.160 (talk) 23:39, 1 April 2008 (UTC)

Your deletions have included deletions of full text peer reviewed articles, so I think your actions are more than some problem to do with pubmed. You have had your edits reverted by numerous editors and admins as either vandalism or as bad edits, not just me, does that not tell you something? The only edits you have made so far is deleting large chunks of data which many editors have spent a lot of time producing from benzodiazepine articles and adding an external link to some article. Animal studies are useful, why do you think scientists and the FDA frequently use them when approving drugs? You can't cut open a living human's head you know and run tests on living brain tissue you know. You know nothing about pubmed obviously. Pubmed contains mostly abstracts of peer reviewed articles because the full articles are available by purchase only. You don't sound like you are familiar with peer reviewed articles. Show me where the idea of wikipedia is to provide a patient information style leaflet like the FDA's fact sheet? Wikipedia if that was the case may as well pack up its bags and just host government bureaucracy public leaflets on its domain. No need for us editors. I don't know why you are so hysterical about all of this, do you not have better things to do with your life instead of going about ripping out huge chunks out of wiki articles. What are your intentions? Do you work for the drug companies? Stop attacking me and stop attacking wikipedia articles. I am not the one behaving badly. You haven't contributed anything to wikipedia apart from deletion of a lot of hard work, not by me but by many other editors.--Stilldoggy (talk) 00:03, 2 April 2008 (UTC)

Just for the record not all substances/compounds are haptens. Not all compounds produce an immune response in normal circumstances. A very small number of people develop an immune response from benzodiazepines, I have had a patient who was allergic to diazepam, a benzodiazepine before.--Stilldoggy (talk) 00:07, 2 April 2008 (UTC)

No, I don't work for the pharm industry. The abstract about haptens was in fact from an immuno assay article. Please note that your inclusions frequently are may be, could be, has been suspected, has been investigated, could explain etc. This is what I call speculative. And maybe your patient was allergic to the tartrazine dye in the pills. Maybe. Maybe not. Anecdotal evidence doesn't belong in wiki either. I believe facts should be included, after having gained some agreed relevance, exceeding the criteria for inclusion in a peer reviewed journal. An encyclopedia is imo not a loose leaf collection of excerpts from arbitrary articles and abstracts. Besides, in developing an immuno assay, you frequently generate an antibody by artificially making a substance a hapten, by attaching a different molecule. But this is the art of creating antibodies, not the pharmacology of the substance in question. Insofar this citation was out of context, as it had nothing to do with allergy, but with the development of urine tests. And quinazolines look a little similar to benzodiazepines, by having two nitrogens in a ring, attached to a benzene ring. This is a six-membered ring however. And you can make derivatives, similar to benzodiazepines from that system. Thats their relation. However, that is not relevant to the pharmacology of benzodiazepines. It is relevant to structure/activity relationships of compounds, having a nitrogen containing ring attached to a benzene ring. So to say, the activity of Qualuude is not relevant to the pharmacology of Librium and doesn't belong there. This is what I call a spurious association. I just didn't like how the wiki article was bloating with may-bes, ending so much different from a pharmacology text book. —Preceding unsigned comment added by 70.137.178.160 (talk) 00:44, 2 April 2008 (UTC)

Hi, The allergy in the lady to diazepam became more pronounced after switching from tablet form to liquid form. I have removed haptens from the article and can see your point how it is not relevant to this article. A quaalude is a sedative hypnotic drug which works similarly to benzodiazepines but not identically. Mandrax is a common brand name. I will review my edits to the pharmacology section of this article and see if I can fix some of it. Maybe try and make it less speculative and more relevant to the majority of readers. I guess you got angry with some of my edits and I got angry that you deleted large chunks of data without warning. Perhaps we can come to some sort of an agreement and sort this out diplomatically.--Stilldoggy (talk) 02:35, 2 April 2008 (UTC)

I have done some pretty extensive pruning of the article, hopefully everyone will be more happy with it now.--Stilldoggy (talk) 04:04, 2 April 2008 (UTC)

Qualuude, namely Methaqualone is kind of a quinazoline analog of benzodiazepines. Look at the structure formulas and compare. In your reference quinazolines were compared to benzos in mouse experiments. You concluded that they are "related". They are, but only in the framework of SAR of compounds with a 2-nitrogen ring attached to a benzene ring - not in the framework of the pharmacology of Librium. So this didn't belong here. Also look at the claim of "neurotoxicity", look closely what they meant. FDA wouldn't have approved the drug if it were neurotoxic in normal use. Neurotoxicity after dipping brain slices into a conc. solution of the agent is not surprising or relevant. Inhibition of acetylcholine release as an effect of the modulation of the GABA system is not a big surprise, as the GABA system is inhibitory after all. It is maybe a likely (!) explanation of anti-seizure, calming, hypnotic, amnestic effects, which overlap a little with those of Scopolamine, the classic sedative, and an explanation for paradoxical side effects on senile old people. But is it relevant? Your reference about hapten really had to do with the construction of antibodies against it, by attachment of other molecules to make it a hapten - the art of antibody construction, irrelevant to Librium pharmacology, but relevant to the manufacture of piss test strips. That was what your reference was about. Allergy seems not to be an important reported side effect. Makes me think of FD&C yellow, as I said. The anecdotal single patient evidence you mentioned reminds me of an old article of the "Journal of Irreproducible Results", where the "scientists" carried out all their experiments on a single old mare "Liesl", until she got extremely upset, then resilient, and deceased. Consequently the "investigation" had to be ended. The "high abuse liability" - there you jumped to conclusions from a reference about the separation of benzos in urine tests. This has nothing to do with abuse liability, except that it proves that it IS being abused. However, FDA/DEA places it in Schedule IV, "low-moderate" abuse liability, and this is an agreed conclusion, after many pros and cons in peer reviewed journals. Finally, I am not a vandal. I should maybe get a life. I do know what peer reviewed materials are, and where to place them. But my well meant intention was to shave your bloated article a little with Occam's razor, and to encourage you reading the context of your reference, before inclusion. Your inclusions were too much blindly, bot-like, "by association". This is kind of vandalism too, and particularly treacherous, as it looks genuinely scientific to the lay reader. Besides, there is a bot, which writes automatically contributions like yours, simply by keyword extraction, but it absolutely makes no sense. Did you use that for a linguistic experiment? 70.137.178.160 (talk) 04:13, 2 April 2008 (UTC)

Conversation was continued on Chlordiazepoxide Talk Page and finished.--Stilldoggy (talk) 09:05, 2 April 2008 (UTC)

[edit] Dispute

Dispute POV pushing for removal of anecdotal material and speculative material. Dispute neutrality of article. 70.137.178.160 (talk) 00:23, 3 April 2008 (UTC)

I dispute your neutrality and real intentions on here. I see that you are attacking me on the temazepam talk page an article I was not a heavy contributer to.--Literaturegeek (talk) 01:17, 4 April 2008 (UTC)

Tell ya what anon user, lets try and compromise. Tell me what parts of the clonazepam article that you have a problem with and I will try to work this out an agreement. This has gone on long enough. Lets all calm down. I know that we can comne to some sort of an agreement.--Literaturegeek (talk) 01:40, 6 April 2008 (UTC)

I removed glucuronidation of morphine from the clonazepam article as I agree its relevance to humans is questionable as the results are from a laboratory rat study. As you know I have already gutted the article and removed a lot of stuff from this article as part of my early attempts to resolve this dispute with you (See up page) before it degenerated into world war 3.--Literaturegeek (talk) 11:13, 6 April 2008 (UTC)

[edit] ref[60]

ref 60, severe braindamage in a dead baby. ref from the 70s concludes:

"Etiology and pathogenesis of this syndrome remain unknown. It is suggested, however, that the pathological changes observed might have been caused by the administration soon after birth of anti-epileptic drugs (diphenylhydantoin, clonazepam and nitrazepam)."

In my lay opinion the poor baby may have suffered from a genetic storage disease. Many of these have only been recognized and explained since the 90s, due to progress in molecular biology and genetics. Insofar this ref may be anecdotal and inconclusive and should not be included IMO. 70.137.178.160 (talk) 17:59, 6 April 2008 (UTC)

I am bored with roche benzos. I want you to come and help me clear out Tamiflu and Roaccutane of references that don't fit the criteria that you have set all over these various benzo talk pages. You say you aren't affiliated with Roche and I believe you 100% so I trust that you will embrace this idea with great enthusiasm. ;=) Then I will address your concerns on clonazepam article.--Literaturegeek (talk) 10:11, 21 April 2008 (UTC)

[edit] Benzo Interchange

There is no one number for benzodiazepine interchange because different half lives mean that the ratio of substance used will be different for long term and short term therapeutic purposes even assuming that all people are equal. Since wikipedia isn't really meant to replace a doctor and the information has never been presented in context that suggests it was meant as anything other than a "how much to use" context, I took that line of text out of the article.

If someone else wants to replace it with information that is either more accurate (typical ranges for otherwise healthy people, both for long and short term use purposes) or based on some measurable fact like receptor affinity and/or blood concentrations, that would be great. Otherwise, while it might be an interesting guideline for someone raiding the medicine cabinet, it is not encyclopedic quality information. Zaphraud (talk) 04:24, 14 April 2008 (UTC)

[edit] Usa gov report

I removed the text because it is inaccurate when it says prescribed benzos are rarely abused and addiction is rare due to findings of US gov report. Clonazepam is the 2nd most commonly abused benzodiazepine in the USA and they are more commonly abused than opiates. They are also the most commonly abused pharmaceuticals. [7]--TreasureXNY (talk) 03:03, 11 May 2008 (UTC)

I just checked out the SAMHSA citation, looks good to me. I see in the edit history that you got your edits reverted earlier. It is best though to talk on the talk page before challenging and removing cited data especially if you are new to wikipedia. Just to let you know wikipedia inlinks are case sensitive. The samhsa link in your citation did not work because it's wiki page is in capital letters. I changed the SAMHSA to capital letters on your citation, so don't worry. Most pages are in lowercase though. It is all fixed now.--Literaturegeek | T@1k? 09:02, 11 May 2008 (UTC)

Hi, thanks for your help --TreasureXNY (talk) 01:29, 12 May 2008 (UTC)