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modified on 31 December 2018 at 11:09 ••• 2,130 views

Chlordiazepoxide

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Chlordiazepoxide is a prescription medication used to treat certain anxiety disorders and symptoms of alcohol withdrawal.


Contents

Chlordiazepoxide can be found in

  • A-Poxide
  • Equibral
  • Librax
  • Librium
  • Limbitrol
  • Mitran
Chlordiazepoxide.svg.png
Chlordiazepoxide3d.png
Chlordiazepoxide
Systematic (IUPAC) name
7- chloro- 2- methylamino- 5- phenyl- 3H- 1,4- benzodiazepine- 4- oxide
Identifiers
CAS number 58-25-3
ATC code N05BA02
PubChem 2712
DrugBank APRD00682
ChemSpider 10248513
Chemical data
Formula C16H14ClN3O 
Mol. mass 299.75 g/mol
Pharmacokinetic data
Bioavailability  ?
Metabolism Hepatic
Half life 5–30 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

D(US)

Legal status

Schedule IV(US)

Routes oral
intramuscular


History of Chlordiazepoxide

Chlordiazepoxide, initially called methaminodiazepoxide was the first benzodiazepine to be synthesised in the mid 1950's. 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 followed by many further benzodiazepine compounds which were introduced over the subsequent years and decades.

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 and dermatologic problems, both of which involve emotional factors, were reduced by chlordiazepoxide.

Chlordiazepoxide enabled the treatment of emotional disturbances without a loss of mental acuity or alertness. It assisted persons burdened by compulsive behavior like one that felt compelled to count the slats on venetian blinds upon entering a room. 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.


Common side effects of chlordiazepoxide

  • Confusion
  • constipation
  • drowsiness
  • fainting
  • increased or decreased 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. 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.


Chlordiazepoxide tolerance and dependence

Tolerance, Chlordiazepoxide

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. 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.

Dependence, Chlordiazepoxide

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.

Chlordiazepoxide taken during pregnancy can cause a postnatal benzodiazepine withdrawal syndrome.