Prazepam

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Prazepam
Prazepam.svg
Prazepam3d.png
Clinical data
Other names9-chloro-2-(cyclopropylmethyl)-6-phenyl-2,5-diazabicyclo[5.4.0]undeca-5,8,10,12-tetraen- 3-one
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MedlinePlus a601036
Routes of
administration 		Oral
ATC code
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Legal status
Pharmacokinetic data
Metabolism Hepatic
Elimination half-life 36–200 hours
Excretion Renal
Identifiers
  • 7-Chloro-1-(cyclopropylmethyl)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one
CAS Number
PubChem CID
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ChEMBL
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ECHA InfoCard 100.019.069 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H17ClN2O
Molar mass 324.81 g·mol−1
3D model (JSmol)
  • Clc4cc\1c(N(C(=O)C/N=C/1c2ccccc2)CC3CC3)cc4
  • InChI=1S/C19H17ClN2O/c20-15-8-9-17-16(10-15)19(14-4-2-1-3-5-14)21-11-18(23)22(17)12-13-6-7-13/h1-5,8-10,13H,6-7,11-12H2 Yes check.svgY
  • Key:MWQCHHACWWAQLJ-UHFFFAOYSA-N Yes check.svgY
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Prazepam is a benzodiazepine derivative drug developed by Warner-Lambert in the 1960s. [2] It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. [3] Prazepam, (Elimination half-life 29-224h), is a prodrug for desmethyldiazepam, (Elimination half-life 36-200h), which is responsible for the therapeutic effects of prazepam. [4]

Contents

Indications

Prazepam is indicated for the short-term treatment of anxiety. After short-term therapy, the dose is usually gradually tapered-off to reduce or avoid any withdrawal or rebound effects. [5] [6] Desmethyldiazepam, an active metabolite, has a very long half-life of 36 to 200 hours, which contributes to the therapeutic effects of prazepam. [7] [8]

Side effects

Side effects of prazepam are less profound than with other benzodiazepines. [9] Excessive drowsiness and with longer-term use, drug dependence, are the most common side effects of prazepam. [10] [11] Side effects such as fatigue or "feeling spacey" can also occur but less commonly than with other benzodiazepines. Other side effects include feebleness, clumsiness or lethargy, clouded thinking and mental slowness. [12] [13] [14]

Tolerance, dependence and withdrawal

Tolerance and dependence can develop with long-term use of prazepam, and upon cessation or reduction in dosage, then a benzodiazepine withdrawal syndrome may occur with symptoms such as tremulousness, dysphoria, psychomotor agitation, tachycardia and sweating. In severe cases, hallucinations, psychosis and seizures can occur. Withdrawal-related psychosis is generally unresponsive to antipsychotic mediations. The risk and severity of the withdrawal syndrome increases the higher the dose and the longer prazepam is taken for. [15] Tolerance, dependence and withdrawal problems may be less severe than with other benzodiazepines, such as diazepam. [16] It may be because tolerance is slower to develop with prazepam than with other benzodiazepines. [17] Abrupt or over-rapid discontinuation of prazepam after long-term use, even at low dosage, may result in a protracted withdrawal syndrome. [18]

Benzodiazepines can induce serious problems of addiction, which is one of the main reasons for their use being restricted to short-term use. A survey in Senegal found that the majority of doctors believed that their training in this area was generally poor. It was recommended that national authorities take urgent action regarding the rational use of benzodiazepines. Almost one-fifth of doctors ignored prescription guidelines regarding short-term use of benzodiazepines, and almost three-quarters of doctors regarded their training and knowledge of benzodiazepines to be inadequate. More training regarding benzodiazepines has been recommended for doctors. [19] [20]

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. [21]

Mechanism of action

Prazepam exerts its therapeutic effects primarily via modulating the benzodiazepine receptor which in turn enhances GABA function in the brain. [22] Prazepam like other benzodiazepines has anticonvulsant properties, but its anticonvulsant properties are not as potent as other benzodiazepines when tested in animal studies. [23] [24] [25] [26]

Pharmacokinetics

Prazepam is metabolised into descyclopropylmethylprazepam (also known as desmethyldiazepam) and 3-hydroxyprazepam which is further metabolised into oxazepam. [27] [28] [29] [30] [31] Prazepam is a prodrug for descyclopropylmethylprazepam/desmethyldiazepam (also known as norprazepam or nordazepam) which is responsible for most of the therapeutic activity of prazepam rather than prazepam itself. [15] [22] [32] [33]

Interactions

Prazepam may interact with cimetidine. [34] Alcohol in combination with prazepam increases the adverse effects, particularly performance impairing side effects and drowsiness. [35]

Overdose

The symptoms of an overdose of prazepam include sleepiness, agitation and ataxia. Hypotonia may also occur in severe cases. Overdoses in children typically result in more severe symptoms of overdose. [36]

Abuse potential

Prazepam like other benzodiazepines has abuse potential and can be habit forming. However, its abuse potential may be lower than other benzodiazepines because it has a slow onset of action. [15] [37]

Toxicity

Animal studies have found prazepam taken during pregnancy results in delayed growth and causes reproductive abnormalities. [38] [39] [40]

Trade names

Common trade names include Centrac, Centrax, Demetrin, Lysanxia, Mono Demetrin, Pozapam, Prasepine, Prazene, Reapam and Trepidan. Trade names vary depending on the country; Austria: Demetrin, Belgium: Lysanxia, France: Lysanxia, Germany: Demetrin; Mono Demetrin, Greece: Centrac, Ireland: Centrax, Italy: Prazene; Trepidan, Macedonia: Demetrin, Prazepam, Netherlands: Reapam, Portugal: Demetrin, South Africa: Demetrin, Switzerland: Demetrin, Thailand: Pozapam; Prasepine. [41]

See also

Related Research Articles

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<span class="mw-page-title-main">Alprazolam</span> Benzodiazepine medication

Alprazolam, sold under the brand name Xanax among others, is a fast-acting, potent tranquilizer of moderate duration within the triazolobenzodiazepine group of chemicals called benzodiazepines. Alprazolam is most commonly prescribed in the management of anxiety disorders, especially panic disorder and generalized anxiety disorder (GAD). Other uses include the treatment of chemotherapy-induced nausea, together with other treatments. GAD improvement occurs generally within a week. Alprazolam is generally taken orally.

<span class="mw-page-title-main">Lorazepam</span> Benzodiazepine medication

Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and chemotherapy-induced nausea and vomiting. It is also used during surgery to interfere with memory formation, to sedate those who are being mechanically ventilated, and, along with other treatments, for acute coronary syndrome due to cocaine use. It can be given orally, transdermally, intravenously (IV), or intramuscularly When given by injection, onset of effects is between one and thirty minutes and effects last for up to a day.

<span class="mw-page-title-main">Clonazepam</span> Benzodiazepine medication

Clonazepam, sold under the brand name Klonopin among others, is a benzodiazepine medication used to prevent and treat anxiety disorders, seizures, bipolar mania, agitation associated with psychosis, obsessive–compulsive disorder (OCD), and akathisia. It is a long-acting tranquilizer of the benzodiazepine class. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. It is typically taken orally but is also used intravenously. Effects begin within one hour and last between eight and twelve hours in adults.

<span class="mw-page-title-main">Bromazepam</span> Benzodiazepine drug

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<span class="mw-page-title-main">Nordazepam</span> Benzodiazepine derivative medication

Nordazepam is a 1,4-benzodiazepine derivative. Like other benzodiazepine derivatives, it has amnesic, anticonvulsant, anxiolytic, muscle relaxant, and sedative properties. However, it is used primarily in the treatment of anxiety disorders. It is an active metabolite of diazepam, chlordiazepoxide, clorazepate, prazepam, pinazepam, and medazepam.

<span class="mw-page-title-main">Clorazepate</span> Benzodiazepine medication

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<span class="mw-page-title-main">Adinazolam</span> Triazolobenzodiazepine drug

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<span class="mw-page-title-main">Ketazolam</span> Chemical compound

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<span class="mw-page-title-main">Camazepam</span> Chemical compound

Camazepam is a benzodiazepine psychoactive drug, marketed under the brand names Albego, Limpidon and Paxor. It is the dimethyl carbamate ester of temazepam, a metabolite of diazepam. While it possesses anxiolytic, anticonvulsant, skeletal muscle relaxant and hypnotic properties it differs from other benzodiazepines in that its anxiolytic properties are particularly prominent but has comparatively limited anticonvulsant, hypnotic and skeletal muscle relaxant properties.

<span class="mw-page-title-main">Etizolam</span> Benzodiazepine analog drug

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<span class="mw-page-title-main">Clotiazepam</span> Chemical compound

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<span class="mw-page-title-main">Brotizolam</span> Benzodiazepine

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<span class="mw-page-title-main">Bretazenil</span> Chemical compound

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<span class="mw-page-title-main">Chlordiazepoxide</span> Benzodiazepine medication

Chlordiazepoxide, sold under the brand 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, benzodiazepines, and other drugs.

<span class="mw-page-title-main">DMCM</span> Chemical compound

DMCM is a drug from the β-carboline family that induces anxiety and convulsions by acting as a negative allosteric modulator of GABAA receptors — functionally opposite to benzodiazepines and related drugs which are positive allosteric modulators — and is used in scientific research for these properties to test new anxiolytic and anticonvulsant medications, respectively. It has also been shown to produce analgesic effects in animals, which is thought to be the drug's induced panic reducing the perception of pain.

<span class="mw-page-title-main">Benzodiazepine withdrawal syndrome</span> Signs and symptoms due to benzodiazepine discontinuation in physically dependent persons

Benzodiazepine withdrawal syndrome is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines as prescribed develops a physical dependence on them and then reduces the dose or stops taking them without a safe taper schedule.

<span class="mw-page-title-main">Delorazepam</span> Benzodiazepine medication

Delorazepam, also known by the synonyms chlordesmethyldiazepam and nordiclazepam, is a drug which is a benzodiazepine and a derivative of desmethyldiazepam. It is marketed in Italy, where it is available under the trade name EN and Dadumir. Delorazepam (chlordesmethyldiazepam) is also an active metabolite of the benzodiazepine drugs diclazepam and cloxazolam. Adverse effects may include hangover type effects, drowsiness, behavioural impairments and short-term memory impairments. Similar to other benzodiazepines delorazepam has anxiolytic, skeletal muscle relaxant, hypnotic and anticonvulsant properties.

Post-acute withdrawal syndrome (PAWS) is a hypothesized set of persistent impairments that occur after withdrawal from alcohol, opiates, benzodiazepines, antidepressants, and other substances. Infants born to mothers who used substances of dependence during pregnancy may also experience a PAWS. While PAWS has been frequently reported by those withdrawing from opiate and alcohol dependence, the research has limitations. Protracted benzodiazepine withdrawal has been observed to occur in some individuals prescribed benzodiazepines.

<span class="mw-page-title-main">Benzodiazepine dependence</span> Medical condition

Benzodiazepine dependence defines a situation in which one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite harmful effects, and maladaptive pattern of substance use, according to the DSM-IV. In the case of benzodiazepine dependence, the continued use seems to be typically associated with the avoidance of unpleasant withdrawal reaction rather than with the pleasurable effects of the drug. Benzodiazepine dependence develops with long-term use, even at low therapeutic doses, often without the described drug seeking behavior and tolerance.

References

  1. ↑ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
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  40. ↑ Guerriero FJ, Fox KA (May 1975). "Benzodiazepine-induced suppression of estrous cycles in C57BL/6J mice". Research Communications in Chemical Pathology and Pharmacology. 11 (1): 155–158. PMID   239442.
  41. ↑ "Benzodiazepine Names". non-benzodiazepines.org.uk. Archived from the original on 2008-12-08. Retrieved 2009-05-31.
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