Nordazepam (
INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
; 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
Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use ...
,
anticonvulsant,
anxiolytic
An anxiolytic (; also antipanic or antianxiety 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 anxiet ...
,
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 therap ...
, and
sedative properties. However, it is used primarily in the treatment of
anxiety disorders. It is an
active metabolite An active metabolite is an active form of a drug after it has been processed by the body.
Metabolites of drugs
An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...
of
diazepam
Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, ...
,
chlordiazepoxide
Chlordiazepoxide, trade name Librium among others, is a sedative and hypnotic medication of the benzodiazepine class; it is used to treat anxiety, insomnia and symptoms of withdrawal from alcohol and other drugs.
Chlordiazepoxide has a medium t ...
,
clorazepate
Clorazepate, sold under the brand name Tranxene among others, is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. Clorazepate is an unusually long-lasting benzodiaz ...
,
prazepam
Prazepam is a benzodiazepine derivative drug developed by Warner-Lambert in the 1960s. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Prazepam is a prodrug for desmethyldiazepam which is responsible fo ...
,
pinazepam
Pinazepam (marketed under the brand name Domar and Duna) is a benzodiazepine drug. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties.
Pinazepam and its metabolite ''N''-desmethyldiazepam are transferred ...
, and
medazepam
Medazepam is a drug that is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative, and skeletal muscle relaxant properties. It is known by the following brand names: Azepamid, Nobrium, Tranquirax (mixed with bevonium) ...
.
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 and insomnia and in the control of symptoms of alcohol withdrawal syndrome.
It is a metabolite of diazepam, prazepam, and temazepam, and ha ...
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 asleep ...
, 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 a potential manifestation of many different diseases ...
, 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
In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary ...
psychiatric disorders
A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...
.
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, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...
at the
GABAA 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 gender 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).
]
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.
See also
* Benzodiazepine
* Benzodiazepine dependence
* Benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome often abbreviated to benzo withdrawal or BZD withdrawal is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines, either medically or recreationally develops a p ...
* Long-term effects of benzodiazepines
References
External links
Inchem - Nordazepam
{{GABAAR PAMs
Benzodiazepines
Lactams
Chloroarenes
GABAA receptor positive allosteric modulators
Human drug metabolites