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a tranquilizer (trade names Librium and Libritabs) used in the treatment of alcoholism (同)Librium, Libritabs

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/08/23 16:24:26」(JST)

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Chlordiazepoxide^[1] ( /ˌklɔərdaɪ.əzɨˈpɒksaɪd/), is a sedative/hypnotic drug and benzodiazepine. It is marketed under the trade names Angirex, Elenium, Klopoxid, Librax (also contains clidinium bromide), Libritabs, Librium, Mesural, Multum, Novapam, Risolid, Silibrin, Sonimen and Tropium.

Chlordiazepoxide was the first benzodiazepine to be synthesised and the discovery of chlordiazepoxide was by pure chance.^[2] 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.^[3]

Chlordiazepoxide has a medium to long half-life but its active metabolite has a very long half-life. The drug has amnestic, anxiolytic, hypnotic and skeletal muscle relaxant properties.^[4]

1 History
2 Indications
3 Contraindications
- 3.1 Pregnancy
4 Side effects
- 4.1 Tolerance and dependence
  - 4.1.1 Tolerance
  - 4.1.2 Dependence
5 Overdose
6 Pharmacology
7 Pharmacokinetics
8 Interactions
9 Recreational use
- 9.1 Legal status
10 Toxicity
- 10.1 Animal
11 Availability
12 Trade names
- 12.1 Combination Drugs
13 Chemistry
14 See also
15 References
16 External links

History

Chlordiazepoxide (initially called methaminodiazepoxide) was the first benzodiazepine to be synthesised in the mid-1950s. Chlordiazepoxide was synthesised from work on a chemical dye, quinazolone-3-oxides. It was discovered by accident when in 1957 tests revealed that the compound had hypnotic, anxiolytic and muscle relaxant effects. Three years later chlordiazepoxide was marketed as a therapeutic benzodiazepine medication under the brand name Librium. Following chlordiazepoxide, in 1963 diazepam hit the market under the brand name Valium - and was followed by many further benzodiazepine compounds over the subsequent years and decades.^[5]

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, rats, cats, and dogs. Fear and aggression were eliminated in much smaller doses than those necessary to produce hypnosis. Chlordiazepoxide is similar to phenobarbital in its anticonvulsant properties. However, it lacks the hypnotic effects of barbiturates. Animal tests were conducted in the Boston Zoo and the San Diego Zoo. Forty-two hospital patients admitted for acute and chronic alcoholism, and various psychoses and neuroses were treated with chlordiazepoxide. In a majority of the patients, anxiety, tension, and motor excitement were "effectively reduced." The most positive results were observed among alcoholic patients. It was reported that ulcers^{[disambiguation needed]} and dermatologic problems, both of which involve emotional factors, were reduced by chlordiazepoxide.^[6]

Chlordiazepoxide enabled the treatment of emotional disturbances without a loss of mental acuity or alertness. It assisted persons burdened by compulsive behavior (e.g. feeling compelled to count the slats on venetian blinds upon entering a room).^[7] In 1963, approval for use was given to diazepam (Valium), a "simplified" version of chlordiazepoxide, primarily to counteract anxiety symptoms. Sleep-related problems were treated with nitrazepam (Mogadon), which was introduced in 1965, temazepam (Restoril), which was introduced in 1969, and flurazepam (Dalmane), which was introduced in 1973.^[8]

Indications

Chlordiazepoxide is indicated for the short term (2–4 weeks) treatment of anxiety which is severe and disabling or subjecting the person to unacceptable distress. It is also indicated as a treatment for the management of acute alcohol withdrawal syndrome.^[9]

Contraindications

Use of chlordiazepoxide should be avoided in individuals with the following conditions:

Myasthenia gravis
Acute intoxication with alcohol, narcotics, or other psychoactive substances
Ataxia
Severe hypoventilation
Acute narrow-angle glaucoma
Severe liver deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of 2)
Severe sleep apnea
Hypersensitivity or allergy to any drug in the benzodiazepine class

Chlordiazepoxide is generally considered an inappropriate benzodiazepine for the elderly due to its long elimination half-life and the risks of accumulation.^[10] Benzodiazepines require special precaution if used in the elderly, pregnancy, children, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.^[11]

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 first trimester of pregnancy. Chlordiazepoxide and diazepam 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, abortion, malformation, intrauterine growth retardation, functional deficits, carcinogenesis and mutagenesis. Caution is also advised during breast feeding as chlordiazepoxide passes into breast milk.^[12]^[13]

Side effects

Common side effects of chlordiazepoxide include:^[14]

Confusion
Constipation
Drowsiness
Fainting
Altered sex drive
Liver problems
Lack of muscle coordination
Minor menstrual irregularities
Nausea
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.^[15] It was later found that scopolamine impairment in learning was caused by an increase in benzodiazapine/GABA activity (and that benzodiapines were not associated with the cholinergic system). ^[16]In tests of various benzodiazepine compounds, chlordiazepoxide was found to cause the most profound reduction in the turnover of 5HT (serotonin) 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.^[17]

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 mouse forebrain.^[18] The Committee of Review of Medicines who carried out an extensive review of benzodiazepines including chlordiazepoxide found and were in agreement with the Institute of Medicine (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the National Institute on Drug Abuse (USA) that there was little evidence that long term use of benzodiazepines were beneficial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tended to lose their sleep promoting properties within 3–14 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 4 months continuous use due to the development of tolerance.^[19]

Dependence

Chlordiazepoxide can cause physical dependence, addiction and what is known as the benzodiazepine withdrawal syndrome. Withdrawal from chlordiazepoxide or other benzodiazepines often leads to withdrawal symptoms which are similar to those seen with alcohol and barbiturates. 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 via a slow and gradual dose reduction regime.^[20]

Chlordiazepoxide taken during pregnancy can cause a postnatal benzodiazepine withdrawal syndrome.^[21]

Overdose

Pharmacology

Chlordiazepoxide acts on benzodiazepine subreceptors of the main GABA_A receptor and this results in an increased binding of the inhibitory neurotransmitter GABA to the GABA_A receptor thereby producing inhibitory effects on the central nervous system and body similar to the effects of other benzodiazepines.^[23] Chlordiazepoxide is anticonvulsant.^[24] There is preferential storage of chlordiazepoxide in some organs including the heart of the neonate. Absorption by any administered route and the risk of accumulation is significantly increased in the neonate. The withdrawal of chlordiazepoxide during pregnancy and breast feeding is recommended, as chlordiazepoxide rapidly crosses the placenta and also is excreted in breast milk.^[25] Chlordiazepoxide also decreases prolactin release in rats.^[26] Benzodiazepines act via micromolar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibit depolarization-sensitive Calcium uptake in animal nerve terminal preparations.^[27] Chlordiazepoxide inhibits acetylcholine release in mouse hippocampal synaptosomes in vivo. This has been found by measuring sodium-dependent high affinity choline uptake in vitro after pretreatment of the mice in vivo with chlordiazepoxide. This may play a role in chlordiazepoxide's anticonvulsant properties.^[28]

Pharmacokinetics

Chlordiazepoxide is a long acting benzodiazepine drug. The half-life of Chlordiazepoxide is 5 – 30 hours but has an active benzodiazepine metabolite (desmethyldiazepam) which has a half-life of 36 – 200 hours.^[29] 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.^[30]

Interactions

Some of the major interactions involving Chlordiazepoxide are listed below.^[31]

ACE inhibitors, Adrenergic neurone blockers, Angiotensin II receptor antagonists, Beta blockers, Calcium channel blockers, Clonidine, Diazoxide, Diuretics, Hydralazine, Methyldopa, Minoxidil, Nitrates, Sodium Nitroprusside - enhanced hypotensive effect
Alcohol, barbiturates, opiates, antihistamines, antipsychotics - increased sedative effect in combination with benzodiazapines.
Cimetidine - metabolism of benzodiazepines inhibited by cimetidine (increased plasma concentration)
Disulfiram - metabolism of benzodiazepines inhibited by disulfiram (increased sedative effects)
Fluvoxamine - plasma concentration of some benzodiazepines increased by fluvoxamine
Levodopa - benzodiazepines possibly antagonise effects of levodopa
Moxonidine - sedative effects possibly increased when benzodiazepines given with moxonidine
Olanzapine - increased risk of hypotension, bradycardia and respiratory depression when parenteral benzodiazepines given with intramuscular olanzapine
Phenytoin - benzodiazepines possibly increase or decrease plasma concentration of phenytoin
Rifampicin - metabolism of benzodiazepines possibly accelerated by rifampicin (reduced plasma concentration)
Sodium Oxybate - benzodiazepines enhance effects of sodium oxybate (avoid concomitant use)

Recreational use

Legal status

Internationally, chlordiazepoxide is a Schedule IV controlled drug under the Convention on Psychotropic Substances.[1]

Toxicity

Animal

Laboratory tests assessing the toxicity of chlordiazepoxide, nitrazepam and diazepam on mice spermatozoa 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.^[36]

Availability

Chlordiazepoxide is available in 5 mg, 10 mg and 25 mg strengths.

Trade names

Combination Drugs

Librax - chlordiazepoxide and clidinium
Apo-Chlorax - chloridazepoxide and clidinium
Libotryp, Limbitrol - chlordiazepoxide and amitriptyline
Clindex - chloridazepoxide and clidinium

Chemistry

Chlordiazepoxide is synthesized from 2-amino-5-chlorobenzophenone. This is reacted in the usual manner with hydroxylamine, forming 2-amino-5-chlorobenzophenone oxide, which upon reaction with chloroacetic acid chloride in acetic acid easily cyclizes to 6-chloro-2-chloromethyl-4-phenylquinazolin-3-oxide. Reacting this with a primary amine, methylamine in particular, leads to an interesting rearrangement (with a ring expansion), and the reaction product turns out to be 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepin-4-oxide. An analogous rearrangement with a ring expansion also proceeds upon reaction with alkaline or alkoxides; however, it should be noted that with dialkylamines, the reaction forms the expected substitution products, 2-dialkylaminomethyl derivatives of 6-chloro- 4-phenylquinazolin-3-oxide.

L.H. Sternbach, U.S. Patent 2,893,992 (1959).
G. Muller, J. Warnant, DE 1096363 (1959).
Sternbach, L. H.; Reeder, E. (1961). Journal of Organic Chemistry 26 (4): 1111. doi:10.1021/jo01063a034. edit

References

^ US Patent 2893992
^ Ban, TA. (2006). "The role of serendipity in drug discovery.". Dialogues Clin Neurosci 8 (3): 335–44. PMC 3181823. PMID 17117615. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3181823.
^ Marshall, KP.; Georgievskava, Z.; Georgievsky, I. (Jun 2009). "Social reactions to Valium and Prozac: a cultural lag perspective of drug diffusion and adoption.". Res Social Adm Pharm 5 (2): 94–107. doi:10.1016/j.sapharm.2008.06.005. PMID 19524858.
^ Liljequist R; Palva E, Linnoila M (1979). "Effects on learning and memory of 2-week treatments with chlordiazepoxide lactam, N-desmethyldiazepam, oxazepam and methyloxazepam, alone or in combination with alcohol". Int Pharmacopsychiatry 14 (4): 190–8. PMID 42628.
^ Cooper, Jack R; Floyd E. Bloom, Robert H. Roth (January 15, 1996) (in Eng). The Complete Story of the Benzodiazepines (seventh ed.). USA: Oxford University Press. ISBN 0-19-510399-8. http://www.etfrc.com/benzos1.htm. Retrieved 7 Apr 2008.
^ New York Times (28 February 1960). "Help For Mental Ills (Reports on Tests of Synthetic Drug Say The Results are Positive)". USA: New York Times. p. E9.
^ New York Times (28 August 1960). "Makers Worried On Tranquilizers". USA: New York Times. p. F1.
^ Sternbach LH (1972). "The discovery of librium". Agents Actions 2 (4): 193–6. doi:10.1007/BF01965860. PMID 4557348.
^ British National Formulary; Committee on Safety of Medicines (April 8, 2008). "CHLORDIAZEPOXIDE HYDROCHLORIDE". BNF.org. http://bnf.org/bnf/bnf/55/3177.htm. Retrieved 8 April 2008.
^ Liu, GG.; Christensen, DB. (2002). "The continuing challenge of inappropriate prescribing in the elderly: an update of the evidence.". J Am Pharm Assoc (Wash) 42 (6): 847–57. doi:10.1331/108658002762063682. PMID 12482007.
^ Authier, N.; Balayssac, D.; Sautereau, M.; Zangarelli, A.; Courty, P.; Somogyi, AA.; Vennat, B.; Llorca, PM. et al. (November 2009). "Benzodiazepine dependence: focus on withdrawal syndrome.". Ann Pharm Fr 67 (6): 408–13. doi:10.1016/j.pharma.2009.07.001. PMID 19900604.
^ Iqbal, MM.; Aneja, A.; Fremont, WP. (May 2003). "Effects of chlordiazepoxide (Librium) during pregnancy and lactation.". Conn Med 67 (5): 259–62. PMID 12802839.
^ Iqbal, MM.; Sobhan, T.; Ryals, T. (Jan 2002). "Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant.". Psychiatr Serv 53 (1): 39–49. doi:10.1176/appi.ps.53.1.39. PMID 11773648. http://ps.psychiatryonline.org/cgi/content/full/53/1/39.
^ drugs. "Chlordiazepoxide patient advice including side effects". drugs.com. http://www.drugs.com/pdr/chlordiazepoxide.html. Retrieved April 7, 2008.
^ Nabeshima T; Tohyama K, Ichihara K, Kameyama T. (November 1990). "Effects of benzodiazepines on passive avoidance response and latent learning in mice: relationship to benzodiazepine receptors and the cholinergic neuronal system". J Pharmacol Exp Ther. 255 (2): 789–94. PMID 2173758.
^ http://www.ncbi.nlm.nih.gov/pubmed/1316618
^ Antkiewicz-Michaluk L; Grabowska M, Baran L, Michaluk J. (1975). "Influence of benzodiazepines on turnover of serotonin in cerebral structures in normal and aggressive rats". Arch Immunol Ther Exp (Warsz). 23 (6): 763–7. PMID 1241268.
^ Crawley JN; Marangos PJ, Stivers J, Goodwin FK (January 1982). "Chronic clonazepam administration induces benzodiazepine receptor subsensitivity". Neuropharmacology 21 (1): 85–9. doi:10.1016/0028-3908(82)90216-7. PMID 6278355.
^ Committee on the Review of Medicines (March 29, 1980). "Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines". Br Med J. 280 (6218): 910–2. doi:10.1136/bmj.280.6218.910. PMC 1601049. PMID 7388368. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1601049.
^ MacKinnon GL; Parker WA. (1982). "Benzodiazepine withdrawal syndrome: a literature review and evaluation". The American journal of drug and alcohol abuse. 9 (1): 19–33. doi:10.3109/00952998209002608. PMID 6133446.
^ Moretti M; Montali S (Sep-October 1982). "[Fetal defects caused by the passive consumption of drugs]". Pediatr Med Chir 4 (5): 481–90. PMID 6985425.
^ Zevzikovas A; Kiliuviene G, Ivanauskas L, Dirse V. (2002). "[Analysis of benzodiazepine derivative mixture by gas-liquid chromatography]". Medicina (Kaunas). 38 (3): 316–20. PMID 12474705.
^ Skerritt JH; Johnston GA. (May 6, 1983). "Enhancement of GABA binding by benzodiazepines and related anxiolytics". Eur J Pharmacol. 89 (3–4): 193–8. doi:10.1016/0014-2999(83)90494-6. PMID 6135616.
^ Chweh AY; Swinyard EA, Wolf HH, Kupferberg HJ (February 25, 1985). "Effect of GABA agonists on the neurotoxicity and anticonvulsant activity of benzodiazepines". Life Sci 36 (8): 737–44. doi:10.1016/0024-3205(85)90193-6. PMID 2983169.
^ Olive G; Dreux C. (January 1977). "Pharmacologic bases of use of benzodiazepines in peréinatal medicine". Arch Fr Pediatr. 34 (1): 74–89. PMID 851373.
^ Grandison L (1982). "Suppression of prolactin secretion by benzodiazepines in vivo". Neuroendocrinology 34 (5): 369–73. doi:10.1159/000123330. PMID 6979001.
^ Taft WC; DeLorenzo RJ (May 1984). "Micromolar-affinity benzodiazepine receptors regulate voltage-sensitive calcium channels in nerve terminal preparations" (PDF). Proc Natl Acad Sci USA 81 (10): 3118–22. doi:10.1073/pnas.81.10.3118. PMC 345232. PMID 6328498. http://www.pnas.org/cgi/reprint/81/10/3118.pdf.
^ Miller JA; Richter JA (January 1985). "Effects of anticonvulsants in vivo on high affinity choline uptake in vitro in mouse hippocampal synaptosomes". Br J Pharmacol 84 (1): 19–25. PMC 1987204. PMID 3978310. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1987204.
^ Ashton CH. (April 2007). "BENZODIAZEPINE EQUIVALENCY TABLE". http://www.bcnc.org.uk/equivalence.html. Retrieved September 23, 2007.
^ Vozeh S. (November 21, 1981). "[Pharmacokinetic of benzodiazepines in old age]". Schweiz Med Wochenschr. 111 (47): 1789–93. PMID 6118950.
^ British National Formulary. "Chlordiazepoxide interactions". BNF. http://bnf.org/bnf/bnf/55/41001i404.htm. Retrieved 07 A p r 2008.
^ New York Times (30 December 1963). "Warning Is Issued On Tranquilizers". USA: New York Times. p. 23.
^ Garretty DJ; Wolff K, Hay AW, Raistrick D. (January 1997). "Benzodiazepine misuse by drug addicts". Annals of clinical biochemistry. 34 (Pt 1): 68–73. PMID 9022890.
^ Thiébot MH; Le Bihan C, Soubrié P, Simon P. (1985). "Benzodiazepines reduce the tolerance to reward delay in rats". Psychopharmacology (Berl). 86 (1–2): 147–52. doi:10.1007/BF00431700. PMID 2862657.
^ Woolverton WL, Nader MA (December 1995). "Effects of several benzodiazepines, alone and in combination with flumazenil, in rhesus monkeys trained to discriminate pentobarbital from saline". Psychopharmacology (Berl.) 122 (3): 230–6. doi:10.1007/BF02246544. PMID 8748392.
^ Kar RN; Das RK. (1983). "Induction of sperm head abnormalities in mice by three tranquilizers". Cytobios. 36 (141): 45–51. PMID 6132780.

External links

Rx-List.com - Chlordiazepoxide
Inchem.org - Chlordiazepoxide
U.S. National Library of Medicine: Drug Information Portal - Chlordiazepoxide

UpToDate Contents

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1. 中等度および重度のアルコール離脱症候群のマネージメント management of moderate and severe alcohol withdrawal syndromes
2. 外来における医師監督下のアルコール離脱症状の治療 medically supervised alcohol withdrawal in the ambulatory setting
3. ベンゾジアゼピンの中毒および離脱 benzodiazepine poisoning and withdrawal
4. HIV感染患者における薬物乱用および中毒 substance abuse and addiction in hiv infected patients
5. 周術期におけるアルコールの有害な使用の同定およびマネージメント identification and management of unhealthy alcohol use in the perioperative period

English Journal

Chlordiazepoxide and lavender oil alter unconditioned anxiety-induced c-fos expression in the rat brain.

Shaw D, Norwood K, Leslie JC.SourceSchool of Psychology, University of Ulster, Coleraine, Northern Ireland BT52 1SA, UK.
Behavioural brain research.Behav Brain Res.2011 Oct 10;224(1):1-7. Epub 2011 May 27.
Lavender oil has a long history of use for treating anxiety, but only recent research has examined its effects using standard behavioural methods used to test novel drugs. The aim of this study was to investigate the effects of inhaled lavender oil on anxiety related behaviour of rats in the open fi
PMID 21641938

Drug-induced state-dependent learning: review of an operant procedure in rats.

Koek W.SourceDepartments of Psychiatry and Pharmacology, University of Texas Health Science Center, San Antonio, Texas, USA.
Behavioural pharmacology.Behav Pharmacol.2011 Sep;22(5-6):430-40.
Drug discrimination and drug state dependence are often thought to be based on the same drug actions, and to differ only in the doses needed to produce them, with discrimination occurring at low doses and state dependence at high doses. Testing this hypothesis has been hampered by the use of discrim
PMID 21716094

Japanese Journal

Treatment of functional dyspepsia with antianxiety or antidepressive agents : systematic review

HOJO MARIKO,MIWA HIROTO,YOKOYAMA TETSUJI,OHKUSA TOSHIFUMI,NAGAHARA AKIHITO,KAWABE MASATO,ASAOKA DAISUKE,IZUMI YUKO,SATO NOBUHIRO
Journal of gastroenterology 40(11), 1036-1042, 2005-11-01
NAID 10016882720

New Conventional Coated-Wire Ion-Selective Electrodes for Flow-Injection Potentiometric Determination of Chlordiazepoxide

Issa Y. M.,Abdel-Ghani N. T.,Shoukry A. F. [他]
Analytical Sciences 21(9), 1037-1042, 2005
NAID 40006990385

Related Pictures

★リンクテーブル★

リンク元	「クロルジアゼポキシド」
拡張検索	「chlordiazepoxide hydrochloride」

「クロルジアゼポキシド」

Chlordiazepoxide
Systematic (IUPAC) name
	7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide
Clinical data
Trade names	Librium
AHFS/Drugs.com	monograph
MedlinePlus	a682078
Pregnancy cat.	D (US)
Legal status	Schedule IV (US)
Routes	oral; intramuscular
Pharmacokinetic data
Metabolism	Hepatic
Half-life	5–30 hours (Active metabolite desmethyldiazepam 36-200 hours: other active metabolites include temazepam and oxazepam.)
Excretion	Renal
Identifiers
CAS number	58-25-3
ATC code	N05BA02
PubChem	CID 2712
DrugBank	DB00475
ChemSpider	10248513
UNII	6RZ6XEZ3CR
KEGG	D00267
ChEBI	CHEBI:3611
ChEMBL	CHEMBL451
Chemical data
Formula	C16H14ClN3O
Mol. mass	299.75 g/mol
	SMILES Clc1ccc2\N=C(/C[N+](/[O-])=C(\c2c1)c3ccccc3)NC;
	InChI InChI=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) ; Key:ANTSCNMPPGJYLG-UHFFFAOYSA-N ;
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　　[★]

英: chlordiazepoxide
化: 塩酸クロルジアゼポキシド chlordiazepoxide hydrochloride
商: Librium、コンスーン、コントール、バランス
関: ベンゾジアゼピン系

マイナートランキライザー

薬効薬理

バランス散10％

1. 鎮静及び緊張除去作用

本剤は大脳辺縁系、特に海馬、扁桃核に作用することで、各種の実験動物（マウス、ラット、ネコ、イヌ、サル）において強力な鎮静・緊張除去作用を示す。特に攻撃的なサルや脳中隔部を損じて実験的にどう猛化したラットに対して、本剤は静穏化に要する量よりはるかに低い薬量で狂暴性を抑制する特異な馴化効果を示している。正常な意識・行動に影響をほとんど及ぼさずに不安・緊張等の情動異常を改善する4）～6）。

2. 自律神経安定化作用

本剤は大脳辺縁系に作用して、視床下部の機能を調整し、自律神経安定化作用を示す6）7）。

3. 抗痙攣、筋弛緩作用

本剤の経口投与によりマウスでの抗痙攣作用並びにマウス、ネコでの筋弛緩作用が認められている6）。

4. 抗不安、抗ストレス作用

本剤はネコの餌への接近－回避型の葛藤行動に陥らせた実験的神経症に対して、著明に餌とり行動の回復を示した8）。また、ラットを拘束して惹起されるストレス胃潰瘍に対しても、本剤は潰瘍の発生を著しく減少させた9）。

参考

バランス散10％

http://www.info.pmda.go.jp/go/pack/1124028B2050_1_08/1124028B2050_1_08?view=body

「chlordiazepoxide hydrochloride」

　　[★] クロルジアゼポキシド

[0] US Patent 2893992

[1] Ban, TA. (2006). "The role of serendipity in drug discovery.". Dialogues Clin Neurosci 8 (3): 335–44. PMC 3181823. PMID 17117615. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3181823.

[Marshall-2009-2] Marshall, KP.; Georgievskava, Z.; Georgievsky, I. (Jun 2009). "Social reactions to Valium and Prozac: a cultural lag perspective of drug diffusion and adoption.". Res Social Adm Pharm 5 (2): 94–107. doi:10.1016/j.sapharm.2008.06.005. PMID 19524858.

[3] Liljequist R; Palva E, Linnoila M (1979). "Effects on learning and memory of 2-week treatments with chlordiazepoxide lactam, N-desmethyldiazepam, oxazepam and methyloxazepam, alone or in combination with alcohol". Int Pharmacopsychiatry 14 (4): 190–8. PMID 42628.

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chlordiazepoxide