(Difference between pages)

Page 1

Page 1Revision 1

Page 2

Page 2Revision 2

Content deleted Content addedVisualWikitext

Revision as of 11:13, 16 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 477057202 of page Chlordiazepoxide for the Chem/Drugbox validation project (updated: 'DrugBank').		Latest revision as of 23:10, 30 December 2024 edit Slothwizard (talk | contribs)Extended confirmed users1,337 editsNo edit summaryTags: Visual edit Mobile edit Mobile web edit
Line 1:		Line 1:
			{{short description|Benzodiazepine medication}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
			{{cs1 config|name-list-style=vanc|display-authors=6}}
	{{Drugbox		{{Drugbox
	| Verifiedfields = changed		| Watchedfields = changed
			| class = ]
	| verifiedrevid = 460030001
			| verifiedrevid = 477165694
	| IUPAC_name = 7-chloro-2-methylamino-5-phenyl-3''H''-1,4-benzodiazepine-4-oxide''
			| IUPAC_name = 7-Chloro-2-methylamino-5-phenyl-3''H''-1,4-benzodiazepine-4-oxide
	| image = Chlordiazepoxide.svg
			| image = Chlordiazepoxide structure.svg
	| width = 150
	| image2 = Chlordiazepoxide-from-xtal-1982-3D-balls.png		| image2 = Chlordiazepoxide-from-xtal-1982-3D-balls.png
	<!--Clinical data-->		<!--Clinical data-->| tradename = Librium, others
	| tradename = Librium
	| Drugs.com = {{drugs.com|monograph|chlordiazepoxide}}		| Drugs.com = {{drugs.com|monograph|chlordiazepoxide}}
			| pronounce = {{IPAc-en|ˌ|k|l|ɔər|d|aɪ|.|ə|z|ᵻ|ˈ|p|ɒ|k|s|aɪ|d}}
	| MedlinePlus = a682078		| MedlinePlus = a682078
	| pregnancy_US = D		| legal_AU = S4
			| legal_BR = B1
			| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=] |language=pt-BR |publication-date=2023-04-04}}</ref>
			| legal_CA = Schedule IV
	| legal_US = Schedule IV		| legal_US = Schedule IV
			| legal_DE = Rx-only/Anlage III
	| routes_of_administration = oral <br> intramuscular
			| legal_UK = Class C
			| dependency_liability = High<ref name="Edmunds-2013">{{cite book | vauthors = Edmunds M, Mayhew M |year=2013 |title= Pharmacology for the Primary Care Provider |url=https://books.google.com/books?id=8FwdEsvnw8oC&pg=PA545 |edition=4th |publisher= Mosby |page=545 |isbn= 9780323087902 }}</ref>
			| addiction_liability = Moderate
			| routes_of_administration = ], ]
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->| metabolism = ]
			| metabolites = • ]<br> • ]<br>• ]<br> • ]<ref>{{cite journal | vauthors = Greenblatt DJ, Shader RI, MacLeod SM, Sellers EM | title = Clinical Pharmacokinetics of Chlordiazepoxide | journal = Clinical Pharmacokinetics | volume = 3 | issue = 5 | pages = 381–394 | date = 1978 | pmid = 359214 | doi = 10.2165/00003088-197803050-00004 }}</ref>
	| metabolism = ]
	| elimination_half-life = 5&ndash;30 hours (Active metabolite ] 36-200 hours: other active metabolites include ] and ].)		| elimination_half-life = 5–30 hours (Active metabolite ] 36–200 hours: other active metabolites include ])
	| excretion = ]		| excretion = ]
	<!--Identifiers-->		<!--Identifiers-->| IUPHAR_ligand = 3370
	| CASNo_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 58-25-3		| CAS_number = 58-25-3
Line 28:		Line 35:
	| ATC_suffix = BA02		| ATC_suffix = BA02
	| PubChem = 2712		| PubChem = 2712
	| DrugBank_Ref = {{drugbankcite|changed|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank = DB00475		| DrugBank = DB00475
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
Line 41:		Line 48:
	| ChEMBL = 451		| ChEMBL = 451
	<!--Chemical data-->		<!--Chemical data-->| C = 16
			| H = 14
	| C=16 | H=14 | Cl=1 | N=3 | O=1
			| Cl = 1
	| molecular_weight = 299.75 g/mol
			| N = 3
	| smiles = Clc1ccc2\N=C(/C(/)=C(\c2c1)c3ccccc3)NC
			| O = 1
	| InChI = 1/C16H14ClN3O/c1-18-15-10-20(21)16(11-5-3-2-4-6-11)13-9-12(17)7-8-14(13)19-15/h2-9H,10H2,1H3,(H,18,19)
			| smiles = ClC1=CC2=C(N=C(NC)C()=C2C3=CC=CC=C3)C=C1
	| InChIKey = ANTSCNMPPGJYLG-UHFFFAOYAM
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C16H14ClN3O/c1-18-15-10-20(21)16(11-5-3-2-4-6-11)13-9-12(17)7-8-14(13)19-15/h2-9H,10H2,1H3,(H,18,19)		| StdInChI = 1S/C16H14ClN3O/c1-18-15-10-20(21)16(11-5-3-2-4-6-11)13-9-12(17)7-8-14(13)19-15/h2-9H,10H2,1H3,(H,18,19)
Line 52:		Line 59:
	| StdInChIKey = ANTSCNMPPGJYLG-UHFFFAOYSA-N		| StdInChIKey = ANTSCNMPPGJYLG-UHFFFAOYSA-N
	}}		}}
			<!-- Definition and medical uses -->
			'''Chlordiazepoxide''', sold under the brand name '''Librium''' among others, is a ] and ] medication of the ] class. It is used to treat ], ] and symptoms of ] from ], ], and other drugs.
			Chlordiazepoxide has a medium to long ], while its ] has a very long half-life. The drug has ], ], ], ], ], and ] properties.<ref>{{cite journal | vauthors = Liljequist R, Palva E, Linnoila M | title = Effects on learning and memory of 2-week treatments with chlordiazepoxide lactam, N-desmethyldiazepam, oxazepam and methyloxazepam, alone or in combination with alcohol | journal = International Pharmacopsychiatry | volume = 14 | issue = 4 | pages = 190–8 | year = 1979 | pmid = 42628 | doi=10.1159/000468381}}</ref>
			<!-- Definition and medical uses -->
			Chlordiazepoxide was patented in 1958 and approved for medical use in 1960.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=535 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA535 |language=en}}</ref> It was the first benzodiazepine to be synthesized and the discovery of chlordiazepoxide was by pure chance.<ref>{{cite journal | vauthors = Ban TA | title = The role of serendipity in drug discovery | journal = Dialogues in Clinical Neuroscience | volume = 8 | issue = 3 | pages = 335–44 | year = 2006 | doi = 10.31887/DCNS.2006.8.3/tban | pmid = 17117615 | pmc = 3181823 }}</ref> Chlordiazepoxide and other benzodiazepines were initially accepted with widespread public approval, but were followed with widespread public disapproval and recommendations for more restrictive medical guidelines for its use.<ref name="Marshall-2009">{{cite journal | vauthors = Marshall KP, Georgievskava Z, Georgievsky I | title = Social reactions to Valium and Prozac: a cultural lag perspective of drug diffusion and adoption | journal = Research in Social & Administrative Pharmacy | volume = 5 | issue = 2 | pages = 94–107 | date = June 2009 | pmid = 19524858 | doi = 10.1016/j.sapharm.2008.06.005 }}</ref>
			{{TOC limit}}
			==Medical uses==
			Chlordiazepoxide is indicated for the short-term (2&ndash;4 weeks) treatment of ] that is severe and disabling or subjecting the person to unacceptable distress. It is also indicated as a treatment for the management of acute ].<ref name=UKlabelGeneric>{{cite web|title=Chlordiazepoxide 10mg Capsules - Summary of Product Characteristics|url=https://www.medicines.org.uk/emc/medicine/26299|publisher=UK Electronic Medicines Compendium|access-date=23 April 2017|language=en|date=19 December 2012|archive-date=23 April 2017|archive-url=https://web.archive.org/web/20170423152643/https://www.medicines.org.uk/emc/medicine/26299|url-status=dead}}</ref>
			It can sometimes be prescribed to ease symptoms of ] (IBS) combined with ] as a fixed dose medication, ].<ref>{{cite web|title=Chlordiazepoxide|url=https://medlineplus.gov/druginfo/meds/a682078.html|publisher=MedlinePlus Drug Information|language=en|date=February 15, 2017}}</ref>
			==Contraindications==
			Use of chlordiazepoxide should be avoided in individuals with the following conditions:
			* ]
			* Acute intoxication with alcohol, narcotics, or other psychoactive substances
			* ]
			* Severe ]
			* Acute narrow-angle ]
			* Severe liver deficiencies (] and liver ] decrease elimination by a factor of 2)
			* Severe ]
			* Hypersensitivity or allergy to any drug in the ] class
			Chlordiazepoxide is generally considered an inappropriate benzodiazepine for the elderly due to its long ] and the risks of accumulation.<ref>{{cite journal | vauthors = Liu GG, Christensen DB | title = The continuing challenge of inappropriate prescribing in the elderly: an update of the evidence | journal = Journal of the American Pharmaceutical Association | volume = 42 | issue = 6 | pages = 847–57 | year = 2002 | pmid = 12482007 | doi = 10.1331/108658002762063682 }}</ref> Benzodiazepines require special precaution if used in the elderly, pregnancy, children, alcohol- or drug-dependent individuals and individuals with ] ].<ref>{{cite journal | vauthors = Authier N, Balayssac D, Sautereau M, Zangarelli A, Courty P, Somogyi AA, Vennat B, Llorca PM, Eschalier A | title = Benzodiazepine dependence: focus on withdrawal syndrome | journal = Annales Pharmaceutiques Françaises | volume = 67 | issue = 6 | pages = 408–13 | date = November 2009 | pmid = 19900604 | doi = 10.1016/j.pharma.2009.07.001 }}</ref>
			===Pregnancy===
			The research into the safety of benzodiazepines during pregnancy is limited and it is recommended that use of benzodiazepines during pregnancy should be based on whether the benefits outweigh the risks. If chlordiazepoxide is used during pregnancy the risks can be reduced via using the lowest effective dose and for the shortest time possible. Benzodiazepines should generally be avoided during the ] of pregnancy. Chlordiazepoxide and ] are considered to be among the safer benzodiazepines to use during pregnancy in comparison to other benzodiazepines. Possible adverse effects from benzodiazepine use during pregnancy include, ], ], ], functional deficits, ] and ]. Caution is also advised during ] as chlordiazepoxide passes into breast milk.<ref>{{cite journal | vauthors = Iqbal MM, Aneja A, Fremont WP | title = Effects of chlordiazepoxide (Librium) during pregnancy and lactation | journal = Connecticut Medicine | volume = 67 | issue = 5 | pages = 259–62 | date = May 2003 | pmid = 12802839 }}</ref><ref>{{cite journal | vauthors = Iqbal MM, Sobhan T, Ryals T | title = Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant | journal = Psychiatric Services | volume = 53 | issue = 1 | pages = 39–49 | date = January 2002 | pmid = 11773648 | doi = 10.1176/appi.ps.53.1.39 }}</ref>
			==Adverse effects==
			Sedative drugs and sleeping pills, including chlordiazepoxide, have been associated with an increased risk of death.<ref>{{cite journal | vauthors = Kripke DF | title = Mortality Risk of Hypnotics: Strengths and Limits of Evidence | journal = Drug Safety | volume = 39 | issue = 2 | pages = 93–107 | date = February 2016 | pmid = 26563222 | doi = 10.1007/s40264-015-0362-0 | s2cid = 7946506 | url = https://escholarship.org/content/qt08d9f3d5/qt08d9f3d5.pdf?t=nz1gjv | doi-access = free }}</ref> The studies had many limitations, such as possible tendency to overestimate risk, possible confounding by indication with other risk factors and confusing hypnotics with drugs having other indications.
			Common side-effects of chlordiazepoxide include:<ref>{{cite web|url= https://www.drugs.com/pdr/chlordiazepoxide.html|title= Chlordiazepoxide patient advice including side-effects|access-date= April 7, 2008|author= drugs|publisher= drugs.com}}</ref>
			* ]
			* ]
			* ]
			* ]
			* Altered ]
			* Liver problems
			* Lack of muscle coordination
			* Minor menstrual irregularities
			* ]
			* Skin rash or eruptions
			* Swelling due to fluid retention
			* Yellow eyes and skin
			Chlordiazepoxide in laboratory mice studies impairs latent learning. Benzodiazepines impair learning and memory via their action on benzodiazepine receptors, which causes a dysfunction in the cholinergic neuronal system in mice.<ref>{{cite journal | vauthors = Nabeshima T, Tohyama K, Ichihara K, Kameyama T | title = Effects of benzodiazepines on passive avoidance response and latent learning in mice: relationship to benzodiazepine receptors and the cholinergic neuronal system | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 255 | issue = 2 | pages = 789–94 | date = November 1990 | pmid = 2173758 }}</ref> It was later found that impairment in learning was caused by an increase in benzodiazepine/] activity (and that benzodiazepines were not associated with the cholinergic system).<ref>{{cite journal | vauthors = McNamara RK, Skelton RW | title = Assessment of a cholinergic contribution to chlordiazepoxide-induced deficits of place learning in the Morris water maze | journal = Pharmacology Biochemistry and Behavior | volume = 41 | issue = 3 | pages = 529–38 | date = March 1992 | pmid = 1316618 | doi = 10.1016/0091-3057(92)90368-p | s2cid = 42752576 }}</ref> In tests of various benzodiazepine compounds, chlordiazepoxide was found to cause the most profound reduction in the turnover of 5HT (]) in rats. Serotonin is closely involved in regulating mood and may be one of the causes of feelings of depression in rats using chlordiazepoxide or other benzodiazepines.<ref>{{cite journal | vauthors = Antkiewicz-Michaluk L, Grabowska M, Baran L, Michaluk J | title = Influence of benzodiazepines on turnover of serotonin in cerebral structures in normal and aggressive rats | journal = Archivum Immunologiae et Therapiae Experimentalis | volume = 23 | issue = 6 | pages = 763–7 | year = 1975 | pmid = 1241268 }}</ref>
			]
			In September 2020, the US ] (FDA) required the ] for all benzodiazepine medicines to be updated to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.<ref>{{cite web | title=FDA expands Boxed Warning to improve safe use of benzodiazepine drug | website=U.S. ] (FDA) | date=23 September 2020 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-boxed-warning-updated-improve-safe-use-benzodiazepine-drug-class | access-date=23 September 2020}} {{PD-notice}}</ref>
			===Tolerance and dependence===
			====Tolerance====
			Chronic use of benzodiazepines, such as chlordiazepoxide, leads to the development of tolerance, with a decrease in number of benzodiazepine binding sites in mice forebrains.<ref>{{cite journal | vauthors = Crawley JN, Marangos PJ, Stivers J, Goodwin FK | title = Chronic clonazepam administration induces benzodiazepine receptor subsensitivity | journal = Neuropharmacology | volume = 21 | issue = 1 | pages = 85–9 | date = January 1982 | pmid = 6278355 | doi = 10.1016/0028-3908(82)90216-7 | s2cid = 24771398 | author-link = Jacqueline Crawley }}</ref> The Committee of Review of Medicines, who carried out an extensive review of benzodiazepines including chlordiazepoxide, found—and were in agreement with the US ] and the conclusions of a study carried out by the White House Office of Drug Policy and the US ]—that there was little evidence that long-term use of benzodiazepines was beneficial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tended to lose their sleep-promoting properties within 3 to 14 days of continuous use, and in the treatment of anxiety the committee found that there was little convincing evidence that benzodiazepines retained efficacy in the treatment of anxiety after four months' continuous use due to the development of tolerance.<ref>{{cite journal | author = Committee on the Review of Medicines | title = Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. | journal = British Medical Journal | volume = 280 | issue = 6218 | pages = 910–2 | date = March 1980 | pmid = 7388368 | pmc = 1601049 | doi = 10.1136/bmj.280.6218.910 }}</ref>
			====Dependence====
			Chlordiazepoxide can cause ] and what is known as the ]. Withdrawal from chlordiazepoxide or other benzodiazepines often leads to withdrawal symptoms that are similar to those seen with alcohol and ]. The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can, however, occur at standard dosages and also after short-term use. Benzodiazepine treatment should be discontinued as soon as possible through a slow and gradual dose-reduction regime.<ref>{{cite journal | vauthors = MacKinnon GL, Parker WA | title = Benzodiazepine withdrawal syndrome: a literature review and evaluation | journal = The American Journal of Drug and Alcohol Abuse | volume = 9 | issue = 1 | pages = 19–33 | year = 1982 | pmid = 6133446 | doi = 10.3109/00952998209002608 }}</ref>
			Chlordiazepoxide taken during pregnancy can cause a ] ].<ref>{{cite journal | vauthors = Moretti M, Montali S | title = | journal = La Pediatria Medica e Chirurgica | volume = 4 | issue = 5 | pages = 481–90 | date = September 1982 | pmid = 6985425 }}</ref>
			===Overdose===
			{{See also|Benzodiazepine overdose}}
			An individual who has consumed excess chlordiazepoxide may display some of the following symptoms:
			* ] (difficulty staying awake)
			* Mental confusion
			* ]
			* ]
			* Impaired motor functions
			** Impaired reflexes
			** Impaired coordination
			** Impaired balance
			** ]
			** ]
			* ]
			Chlordiazepoxide is typically used under controlled conditions for specific syndromes and sees far less frequent usage when compared to newer drugs of the same class and thus is unlikely to be encountered in a clinical emergency setting as a stand-alone drug causing life-threatening concern. Like other drugs in its class, chlordiazepoxide alongside benzodiazepines as a whole have a lowered potential to cause life-threatening injury - though this does not preclude their common co-contaminant discovery with other depressant drugs of abuse, nor their ability to contribute to an already potentially fatal episode of drug-induced respiratory depression. In cases of suspected overdose, supportive care and observation are most often indicated and provided incrementally in relation to severity and duration of symptoms. ] is uniquely poised as an "antidote" that specifically counteracts damaging ] affect induced via benzodiazepine mechanism of action - though is not generally indicated in relation to the severity of symptoms where other treatment options exist, and often has numerous damaging consequences that must be carefully weighted before any potential administration.<ref>Kang M, Galuska MA, Ghassemzadeh S. Benzodiazepine Toxicity. . In: StatPearls . Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482238/
			</ref>
			==Pharmacology==
			Chlordiazepoxide acts on ] allosteric sites that are part of the GABA<sub>A</sub> receptor/ion-channel complex and this results in an increased binding of the inhibitory neurotransmitter ] to the GABA<sub>A</sub> receptor thereby producing inhibitory effects on the ] and body similar to the effects of other ].<ref>{{cite journal | vauthors = Skerritt JH, Johnston GA | title = Enhancement of GABA binding by benzodiazepines and related anxiolytics | journal = European Journal of Pharmacology | volume = 89 | issue = 3–4 | pages = 193–8 | date = May 1983 | pmid = 6135616 | doi = 10.1016/0014-2999(83)90494-6 }}</ref> Chlordiazepoxide is an ].<ref>{{cite journal | vauthors = Chweh AY, Swinyard EA, Wolf HH, Kupferberg HJ | title = Effect of GABA agonists on the neurotoxicity and anticonvulsant activity of benzodiazepines | journal = Life Sciences | volume = 36 | issue = 8 | pages = 737–44 | date = February 1985 | pmid = 2983169 | doi = 10.1016/0024-3205(85)90193-6 }}</ref>
			Chlordiazepoxide is preferentially stored in some organs including the hearts of neonates. Absorption by any administered route and the risk of accumulation is significantly higher in neonates. The withdrawal of chlordiazepoxide during pregnancy and breast feeding is recommended, as chlordiazepoxide rapidly crosses the placenta and also is excreted in breast milk.<ref>{{cite journal | vauthors = Olive G, Dreux C | title = | journal = Archives Françaises de Pédiatrie | volume = 34 | issue = 1 | pages = 74–89 | date = January 1977 | pmid = 851373 }}</ref> Chlordiazepoxide also decreases prolactin release in rats.<ref>{{cite journal | vauthors = Grandison L | title = Suppression of prolactin secretion by benzodiazepines in vivo | journal = Neuroendocrinology | volume = 34 | issue = 5 | pages = 369–73 | year = 1982 | pmid = 6979001 | doi = 10.1159/000123330 }}</ref> Benzodiazepines act via ] benzodiazepine binding sites as ] channel blockers and significantly inhibit depolarization-sensitive Calcium uptake in animal nerve terminal preparations.<ref>{{cite journal | vauthors = Taft WC, DeLorenzo RJ | title = Micromolar-affinity benzodiazepine receptors regulate voltage-sensitive calcium channels in nerve terminal preparations | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 10 | pages = 3118–22 | date = May 1984 | pmid = 6328498 | pmc = 345232 | doi = 10.1073/pnas.81.10.3118 | bibcode = 1984PNAS...81.3118T | url = http://www.pnas.org/cgi/reprint/81/10/3118.pdf | type = PDF | doi-access = free }}</ref> Chlordiazepoxide inhibits ] release in mouse hippocampal synaptosomes in vivo. This has been found by measuring sodium-dependent high affinity ] uptake in vitro after pretreatment of the mice in vivo with chlordiazepoxide. This may play a role in chlordiazepoxide's anticonvulsant properties.<ref>{{cite journal | vauthors = Miller JA, Richter JA | title = Effects of anticonvulsants in vivo on high affinity choline uptake in vitro in mouse hippocampal synaptosomes | journal = British Journal of Pharmacology | volume = 84 | issue = 1 | pages = 19–25 | date = January 1985 | pmid = 3978310 | pmc = 1987204 | doi = 10.1111/j.1476-5381.1985.tb17368.x }}</ref>
			==Pharmacokinetics==
			Chlordiazepoxide is a long-acting benzodiazepine drug. The half-life of chlordiazepoxide is from 5 to 30 hours but has an active benzodiazepine metabolite, ], which has a half-life of 36 to 200 hours.<ref>{{cite web | url = http://www.bcnc.org.uk/equivalence.html | title = Benzodiazepine equivalency table | access-date = September 23, 2007 | author = Ashton CH. | date = April 2007 | archive-date = September 28, 2007 | archive-url = https://web.archive.org/web/20070928121055/http://www.bcnc.org.uk/equivalence.html | url-status = dead }}</ref> The half-life of chlordiazepoxide increases significantly in the elderly, which may result in prolonged action as well as accumulation of the drug during repeated administration. Delayed body clearance of the long half-life active metabolite also occurs in those over 60 years of age, which further prolongs the effects of the drugs with additional accumulation after repeated dosing.<ref>{{cite journal | vauthors = Vozeh S | title = | journal = Schweizerische Medizinische Wochenschrift | volume = 111 | issue = 47 | pages = 1789–93 | date = November 1981 | pmid = 6118950 }}</ref>
			Despite its name, chlordiazepoxide is not an ].
			==History==
			Chlordiazepoxide (initially called ''methaminodiazepoxide'') was the first benzodiazepine to be synthesized in the mid-1950s. The synthesis was derived from work on a class of dyes, quinazoline-3-oxides.<ref>{{cite journal | vauthors = Sternbach LH | title = The discovery of librium | journal = Agents and Actions | volume = 2 | issue = 4 | pages = 193–6 | date = June 1972 | pmid = 4557348 | doi = 10.1007/BF01965860 | s2cid = 26923026 }}</ref> It was discovered by accident when in 1957 tests revealed that the compound had ], ], and ] effects. "The story of the chemical development of Librium and Valium was told by ]. The serendipity involved in the invention of this class of compounds was matched by the trials and errors of the pharmacologists in the discovery of the tranquilizing activity of the benzodiazepines. The discovery of Librium in 1957 was due largely to the dedicated work and observational ability of a gifted technician, Beryl Kappell. For some seven years she had been screening compounds by simple animal tests for muscle relaxant activity using ] as a standard and then ] and ] when they became available. All compounds submitted by the chemical staff for central nervous activity were screened. It was this battery of tests that picked out RO 5-0690 (Librium, chlordiazepoxide) as being similar but more potent than meprobamate."<ref>{{cite web |url=http://garfield.library.upenn.edu/classics1980/A1980KP91000001.pdf |title=Pharmacological and clinical-studies on valium: a new psychotherapeutic agent of the benzodiazepine class |date=1980-11-24 |access-date=2019-05-23 }}</ref> Three years later chlordiazepoxide was marketed as a therapeutic benzodiazepine medication under the brand name Librium. Following chlordiazepoxide, in 1963 ] hit the market under the brand name Valium—and was followed by many further benzodiazepine compounds over the subsequent years and decades.<ref>{{cite book|url=http://www.etfrc.com/benzos1.htm|title=The Complete Story of the Benzodiazepines | vauthors = Cooper JR, Bloom FE, Roth RH |date=January 15, 1996|publisher=Oxford University Press|isbn=0-19-510399-8|edition=seventh|location=USA|access-date=7 Apr 2008 |url-status=dead |archive-url=https://web.archive.org/web/20080315230230/http://www.etfrc.com/benzos1.htm |archive-date=2008-03-15 }}</ref>
			In 1959 it was used by over 2,000 physicians and more than 20,000 patients. It was described as "chemically and clinically different from any of the tranquilizers, psychic energizers or other psychotherapeutic drugs now available." During studies, chlordiazepoxide induced muscle relaxation and a quieting effect on laboratory animals like mice, ]s, ]s, and ]s. Fear and aggression were eliminated in much smaller doses than those necessary to produce hypnosis. Chlordiazepoxide is similar to ] in its ] properties. However, it lacks the hypnotic effects of ]. Animal tests were conducted in the ] and the ]. Forty-two hospital patients admitted for acute and chronic alcoholism, and various ] and ] were treated with chlordiazepoxide. In a majority of the patients, ], ], and motor excitement were "effectively reduced." The most positive results were observed among ] patients. It was reported that ]s and ] problems, both of which involved emotional factors, were reduced by chlordiazepoxide.<ref>{{cite news | author=The New York Times | title = Help For Mental Ills (Reports on Tests of Synthetic Drug Say The Results are Positive) | work=]| location = USA | page = E9 | date = 28 February 1960 }}</ref>
			In 1963, approval for use was given to ] (Valium), a "simplified" version of chlordiazepoxide, primarily to counteract anxiety symptoms. Sleep-related problems were treated with ] (Mogadon), which was introduced in 1972, ] (Restoril), which was introduced in 1979, and ] (Dalmane), which was introduced in 1975.<ref>{{cite journal | vauthors = Sternbach LH | title = The discovery of librium | journal = Agents and Actions | volume = 2 | issue = 4 | pages = 193–6 | date = June 1972 | pmid = 4557348 | doi = 10.1007/BF01965860 | s2cid = 26923026 }}</ref>
			==Recreational use==
			{{See also|Benzodiazepine drug misuse}}
			In 1963, Carl F. Essig of the ] of the ] stated that ], ], ], ], ] and chlordiazepoxide were drugs whose usefulness “can hardly be questioned.” However, Essig labeled these “newer products” as “drugs of addiction,” like ], whose habit-forming qualities were more widely known. He mentioned a 90-day study of chlordiazepoxide, which concluded that the automobile accident rate among 68 users was 10 times higher than normal. Participants' daily dosage ranged from 5 to 100 milligrams.<ref>{{cite news | author =The New York Times | title = Warning Is Issued On Tranquilizers | work=The New York Times| location = USA | page = 23 | date = 30 December 1963 }}</ref>
			Chlordiazepoxide is a drug of potential ] and is frequently detected in urine samples of drug users who have not been prescribed the drug.<ref>{{cite journal | vauthors = Garretty DJ, Wolff K, Hay AW, Raistrick D | title = Benzodiazepine misuse by drug addicts | journal = Annals of Clinical Biochemistry | volume = 34 | issue = Pt 1 | pages = 68–73 | date = January 1997 | pmid = 9022890 | doi = 10.1177/000456329703400110 | s2cid = 42665843 | doi-access = free }}</ref>
			===Legal status===
			Internationally, chlordiazepoxide is a ] controlled drug under the ].<ref>{{Cite book|title=Psychotropic Substances |publisher=United Nations International Narcotics Control Board|year=2016|isbn=978-92-1-048165-6|location=New York|pages=27}}</ref>
			==Toxicity==
			===Animal===
			Laboratory tests assessing the toxicity of chlordiazepoxide, ] and ] on mice ] found that chlordiazepoxide produced toxicities in sperm including abnormalities involving both the shape and size of the sperm head. Nitrazepam, however, caused more profound abnormalities than chlordiazepoxide.<ref>{{cite journal | vauthors = Kar RN, Das RK | title = Induction of sperm head abnormalities in mice by three tranquilizers | journal = Cytobios | volume = 36 | issue = 141 | pages = 45–51 | year = 1983 | pmid = 6132780 }}</ref>
			==Availability==
			Chlordiazepoxide is available in various dosage forms, alone or in combination with other drugs, worldwide. In combination with ] as NORMAXIN-CC and in combination with dicyclomine as NORMAXIN for IBS, and with the anti-depressant ] as Limbitrol.<ref>Drugs.com Page accessed April 24, 2015
			</ref>
			==See also==
			* ]
			* ]
			* ]
			* ]
			* ]
			==References==
			{{reflist|32em}}
			==External links==
			*
			*
			*
			{{Benzodiazepines}}
			{{Anxiolytics}}
			{{GABAAR PAMs}}
			]
			]
			]
			]