Nordazepam ( INN; marketed under brand names Nordaz, Stilny, Madar, Vegesan, and Calmday; also known as nordiazepam, desoxydemoxepam, and desmethyldiazepam) is a 1,4-benzodiazepine derivative. Like other benzodiazepine derivatives, it has amnesic,

anticonvulsant Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...

anxiolytic An anxiolytic (; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

muscle relaxant A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeu ...

, and

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

properties. However, it is used primarily in the treatment of

anxiety disorder Anxiety disorders are a group of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal functions are significantly impaired. Anxiety may cause phys ...

s. It is an active metabolite of

diazepam Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety disorder, anxiety, seizures, alcohol withdrawal syndr ...

chlordiazepoxide Chlordiazepoxide hydrochloride, sold under the brand name Librium is a sedative and hypnotic medication of the benzodiazepine class. It is used to treat anxiety, insomnia and symptoms of withdrawal from alcohol, benzodiazepines, and other drug ...

, clorazepate, prazepam, pinazepam, and medazepam. Nordazepam is among the longest lasting (longest half-life) benzodiazepines, and its occurrence as a metabolite is responsible for most cumulative side-effects of its myriad of pro-drugs when they are used repeatedly at moderate-high doses; the nordazepam metabolite

oxazepam Oxazepam is a short-to-intermediate-acting benzodiazepine. Oxazepam is used for the treatment of anxiety, insomnia, and to control symptoms of alcohol withdrawal syndrome. It is a metabolite of diazepam, prazepam, and temazepam, and has moderate ...

is also active (and is a more potent, full BZD-site agonist), which contributes to nordazepam cumulative side-effects but occur too minutely to contribute to the cumulative side-effects of nordazepam pro-drugs (except when they are abused chronically in extremely supra-therapeutic doses).

Side effects

Common side effects of nordazepam include

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling aslee ...

, which is more common in elderly patients and/or people on high-dose regimens.

Hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but it is a potential manifestation of many different dis ...

, which is much less common, is also associated with high doses and/or old age.

Contraindications and special caution

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol- or drug-dependent individuals, and individuals with comorbid

psychiatric disorders A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...

. As with many other drugs, changes in liver function associated with aging or diseases such as cirrhosis, may lead to impaired clearance of nordazepam.

Pharmacology

Nordazepam is a

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

at the GABA_A receptor, which makes it less potent than other benzodiazepines, particularly in its amnesic and muscle-relaxing effects. Its elimination half life is between 36 and 200 hours, with wide variation among individuals; factors such as age and sex are known to impact it. The variation of reported half-lives are attributed to differences in nordazepam metabolism and that of its metabolites as nordazepam is hydroxylated to active metabolites such as oxazepam, before finally being glucuronidated and excreted in the urine. This can be attributed to extremely variable hepatic and renal metabolic functions among individuals depending upon a number of factors (including age, ethnicity, disease, and current or previous use/abuse of other drugs/medicines).

Chemistry

Nordazepam is similar to

, except that the methyl group at the R1 position has been replaced with a hydrogen. Nordazepam can be synthesized with 2-amino-5-chlorobenzophenone and

chloroacetyl chloride Chloroacetyl chloride is a chlorinated acyl chloride. It is a bifunctional compound, making it a useful building block chemical. Production Industrially, it is produced by the carbonylation of methylene chloride, oxidation of vinylidene chlo ...

. Nordazepam itself can also be used in the synthesis of diazepam by methylating the R1 position using

dimethyl sulfate Dimethyl sulfate (DMS) is a chemical compound with formula (CH3O)2SO2. As the diester of methanol and sulfuric acid, its formula is often written as ( CH3)2 SO4 or Me2SO4, where CH3 or Me is methyl. Me2SO4 is mainly used as a methylating agen ...

Pregnancy and nursing mothers

Nordazepam, like other benzodiazepines, easily crosses the placental barrier, so the drug should not be administered during the first trimester of pregnancy. In case of serious medical reasons, nordazepam can be given in late pregnancy, but the fetus, due to the pharmacological action of the drug, may experience side effects such as hypothermia, hypotonia, and sometimes mild respiratory depression. Since nordazepam and other benzodiazepines are excreted in breast milk, the substance should not be administered to mothers who are breastfeeding. Discontinuing of breast-feeding is indicated for regular intake by the mother.

Recreational use

Nordazepam and other sedative-hypnotic drugs are detected frequently in cases of people suspected of driving under the influence of drugs. Many drivers have blood levels far exceeding the therapeutic dose range, suggesting benzodiazepines are commonly used in doses higher than the recommended doses.

References

External links

Inchem - Nordazepam
{{GABAAR PAMs Benzodiazepines Lactams Chloroarenes Human drug metabolites