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B is a somewhat generous rating, but the article basically only needs a bit of cleanup. Fuzzform 19:53, 31 May 2007 (UTC)
Cluttered
The article seems to be cluttered with random citations, coming to the wrong conclusions. Example: Chlordiazepoxide is related to quinazolines - by being investigated together with quinazolines in one citation. Chlordiazepoxide is a hapten - by being mentioned together with the word "hapten" in an article about immuno assay tests. These are not peer reviewed facts. These are collections from arbitrary resources which have no relation to the pharmacology of the substance. —Preceding unsigned comment added by 70.137.178.160 (talk) 22:06, 1 April 2008 (UTC)
They are from peer reviewed sources. The quinazoline and hapten is an abstract from a peer reviewed journal, specifically Journal of pharmaceutical sciences. See Please stop vandalising wikipedia articles intentionally or unintentionally with good or bad intentions, just stop going around deleting stuff for no good reason. You have already been warned on your talk page by an admin about doing this.--Stilldoggy (talk) 22:13, 1 April 2008 (UTC)
You conclude that it is related to quinazolines, by being "mentioned together" with quinazolines in this investigation. You claim that it is a hapten, by being mentioned as a hapten in an article about immuno assay tests. Of course it is a hapten there, that is how immuno assays work. Every substance is the hapten in an immuno assay for this substance, you develop an antibody that binds for it, to detect it. But this is not pharmacology of the substance, but the mechanism of an immuno assay test, like urine test strips! Please look at least what the citation is about, before including it. Please have quality control look at this. —Preceding unsigned comment added by 70.137.178.160 (talk) 22:28, 1 April 2008 (UTC) To be specific, the "peer reviewed facts" look like the bot-like inclusion of a pubmed search, without closer inspection of what the article is about, creating a lot of spurious associations, which are irrelevant to the pharmacology of the substance. —Preceding unsigned comment added by 70.137.178.160 (talk) 22:36, 1 April 2008 (UTC)
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! 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, because it is mentioned in a drug abuse article. FDA says low-to-medium abuse liability, placement in Schedule IV. 70.137.178.160 (talk) 23:02, 1 April 2008 (UTC)
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 been made 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? Misplaced Pages 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?--Stilldoggy (talk) 23:55, 1 April 2008 (UTC)
Stilldoggy wrote re Clonazepam: 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.
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. 70.137.178.160 (talk) 01:14, 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) 04:20, 2 April 2008 (UTC)
I have removed the data stating neurotoxicity. I accept your point on hapten's and have deleted hapten from the wiki article. I am going to remove some of the edits that I made as you do have some valid points. I reject strongly your assertion that benzodiazepines are not commonly abused. Here is a quote from a better reference in bold. These drugs have their own addictive potential and are often taken in combination with opiates. Up to 90 per cent of attenders at drug misuse treatment centres reported use of benzodiazepines in a one-year period, 15 and 49 per cent had injected them. That quote comes from a Department Of Health uk government website. If benzodiazepines have a low abuse potential then you have to add in cocaine, heroin and cannabis as having a low to moderate abuse potential on the illicit drug scene. Here is the link to the DOH document on their own website. You need to understand that drugs are not classified solely based on how frequently they are abused, for example cannabis and alcohol are very very commonly abused, cannabis is not a schedule 1 drug and alcohol is legal. Other factors also determine the classification of drugs of abuse include harm to the misuser's health and harm to society, crime, risk and degree of physical or psychological dependency, drug related deaths and so on. In the case of high potency opiates they are much more dangerous in overdose than benzodiazepines which is the main reason and driving force to classify opiates higher than other drugs of addiction. The other main factor was their addictiveness. If you go back in history and study the background of the various drugs of addiction being classified and look up the criteria for classifying drugs you will see that I am correct. So I think in this case it is you who is jumping to conclusions of whether benzos form a big part of the illicit drug scene or not based solely on what schedule they are in. We have both managed to show one another that our edits are not perfect. Maybe we can compromise. Hopefully your next response to me will be more pleasant.--Stilldoggy (talk) 05:43, 2 April 2008 (UTC)
Compared to the huge volume of legitimate use, the abuse is low. Millions of people use them under medical supervision. A few people misuse them, this are the reports from drug centers, mostly mixed abuse with opiates, to increase the narcotic effect. Benzos are able to form an addiction, but their effects are usually not regarded as desirable or euphoric for themselves. Not much better than an old paint thinner cloth, but less stinky. I would stick with the C IV placement, not the stories from the drug centers and their selected clients. These guys would also huff petrol. 70.137.178.160 (talk) 05:59, 2 April 2008 (UTC)
To convince you, look at what William S Burroughs has to say about barbiturates "Nembies" = Nembutal in the old days. It is the lowest stage of addiction, the addicts fall off bar stools, let food fall out of the mouth, are confused, belligerent and stupid. etc. (He talks about junkies who ran out of stuff and use nembies as a substitute because the old monkey is looking over their shoulder) This has seemingly carried over to some benzos, since barbs and qualuudes are not available any more, probably mostly temazepam, clonazepam, (in europe) flunitrazepam (Schedule I in US). The other benzos are not hypnotic enough to be used like that. So your benzo junkies are mostly hungry opiate users, who abuse sleeping pills, like Burroughs described. I would not overgeneralize this to all benzos. 70.137.178.160 (talk) 06:28, 2 April 2008 (UTC)
You can say that about opiates as well. There is a huge amount of legitamate use of opiates as well with millions using opiates legitamately. A similar amount of people abuse opiates as benzodiazepines. I am failing to understand your argument? Here is another reference from another UK government website. It found that benzodiazepines were the second most commonly detected drug among arrested individuals. Only cannabis was more commonly detected. Benzodiazepines were more commonly detected than heroin. I am sorry but I am trying to be diplomatic with you on this talk page and the talk page of clonazepam and have tried to mend fences with you in a way. I have accepted many of your edits and agreed that several of my edits were not well chosen but you come across as having an editing agenda and are making edits which suit your opinion and you are not citing any sources, just delete, delete and ignoring the talk page and my attempt at diplomacy. The department of health and scottish government findings are certainly credible citations, involve humans and are government official reports. You really can't get much more credible sources than that.--Stilldoggy (talk) 06:49, 2 April 2008 (UTC)
I am becoming more and more convinced that you have an agenda. First of all you attack pubmed as being not reliable and screaming to high heaven that only extensive review articles and FDA bureaucracies can be added to wikipedia. Now you are making reference to a single man William S. Burroughs who isn't even a scientist but is a novelist and "social critic". Apparently this is superior to government reports. Benzos are very hypnotic, they are used all the time in hospitals to knock patients out for things like an endoscopy and used along with general anestheics. What are you talking about? I am not a benzo junkie and I have never been an opiate abuser but thanks for the personal attack though.--Stilldoggy (talk) 06:49, 2 April 2008 (UTC)
Should read "your benzo junkies". Not YOU! Not all benzos are very hypnotic. Noctamide, Rivotril, Temazepam, Rohypnol are very hypnotic. The other ones like Librium, Frisium, Ativan are not. They are designed to run around with them during the day. "day-tranquilizers". In deed the abuse problem is limited to "sleeping pills" in "multiple substance" i.e. opiate abusers. If you are so much in favor of the scottish buerocracy, why don't you accept the DEA findings? 70.137.178.160 (talk) 07:04, 2 April 2008 (UTC)
Ativan is sedating and is widely used for sedation in hospitals, it was just marketed as an anxiolytic because the market dictated that there were already enough hypnotics on the market. Librium is long acting and therefore unsuitable as a hypnotic. Frisium is not a 1,4 benzo and anyway it has been marketed as an antiepileptic. Diazepam is currently the most commonly abused benzodiazepine in the uk, it is not a sleeping pill. Xanax is the most commonly abused benzo in the USA and it is not a sleeping pill or marketed as one. The pharmacological properties of day time benzos and night time benzos are the same, they are all benzodiazepine receptor agonists. What DEA findings? You only stated that the DEA classed benzos as schedule IV. I never disputed that. I know that. When did I reject that?--Stilldoggy (talk) 07:13, 2 April 2008 (UTC)
Of course benzos are found more often then heroin in arrests! They are handed out with "no questions asked" by doctors, and my grannie is munching them as candies! Where is your logic? It proves nothing. The agenda of the drug agencies is to put everything under tighter control, including grandmas life savers. But we can't turn everything upside down for a few idiot kids. And obviously you have not compared Rohypnol against Librium yourself. Of course they all act on the benzodiazepine receptor, but with a different profile. Frisium has been marketed as a day tranquilizer in the old days, it really had almost no hypnotic properties. There are subtypes of benzo receptors, as pointed out in Frisium article. They are not the same, it is not just marketing hype. Daytime and nighttime benzos are not the same. DEA findings = C IV, for good reason. 70.137.178.160 (talk) 07:28, 2 April 2008 (UTC)
The classification of benzos as schedule IV drugs is listed here. I vaguely remember doing the edit myself but could be wrong. It is already listed in the article. So I don't reject the DEA's schedule status. Actually benzo prescribing is frowned upon by doctors in the UK and they generally try to avoid prescribing them. UK guidelines state benzos are to be prescribed for 2-4 weeks only. Check the British National Formulary. They ain't handed out like candy here. A quote from your latest post "They are handed out with 'no questions asked' by doctors, and my grannie is munching them as candies! Where is your logic? It proves nothing. The agenda of the drug agencies is to put everything under tighter control, including grandmas life savers. But we can't turn everything upside down for a few idiot kids." As far as I am concerned your post has demonstrated to me that you are of mindset of the prodrug group. This is reflected in your above post and in your editing, such as deleting the entire tolerance section of this article and numerous other edits, arguing every way possible to show the drug in a positive light. You contribute no citations. Your sole intention is to delete, delete and delete selectively content which you don't like. I accept some of my edits were worthy of deletion and I accepted a lot of the amendments that you made but it is becoming increasingly clear that you are obsessive with getting your own way no matter what and no amount of reasoning with you is going to work because you have an agenda. You are not open to diplomacy regarding edits. I am ceasing conversation with you. An admin can settle this. I came to wikipedia to try to help expand articles, I may not have been perfect in my edits but I did not come here to engage in an edit war or an argument with a fanatical prodrug individual. I have been up all night with no sleep trying to sort out and "perfect" these articles for you and wikipedia and now I realise instead of you having genuine concerns about the articles I find that my initial suspicions were confirmed, that you are not here to improve wikipedia but to further your own personal prodrug legalisation beliefs. I am going to bed. I will be having no more contact with you.=--Stilldoggy (talk) 07:41, 2 April 2008 (UTC)
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