TEMAZEPAM (PD000427, SEQDDYPDSLOBDC-UHFFFAOYSA-N)

General

Preferred name

TEMAZEPAM

Synonyms

TEMAZEPAM SULFATE

WY-3917

Temaz

(rs)-temazepam

Restoril

Temazepam civ

Normison

NSC-246303

Kentepam

Temazepam-d8

Temazepam-d5 (CRM)

Temazepam-d5

Temazepam-d8 (exempt preparation)

TPX-0005

P&D ID

PD000427

CAS

846-50-4

2747917-64-0

136765-51-0

1802220-02-5

Tags

natural product

drug

available

Approved by

FDA

First approval

1981

Drug Status

investigational

approved

withdrawn

Drug indication

Tranquilizer (minor)

Insomnia

Max Phase

Phase 4

Structure

Probe scores

P&D probe-likeness score

[[ v.score ]]%

Structure formats

[[ format ]]

[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]

Description

(extracted from source data)

ROE Following a single dose, 80-90% of the dose appears in the urine, predominantly as the O-conjugate metabolite, and 3-13% of the dose appears in the faeces [FDA Label] [F3718, L5539]. Less than 2% of the dose is excreted unchanged or as N-desmethyltemazepam in the urine [FDA Label] [F3718, L5539].

INDICATION Temazepam is specifically indicated only for the short-term management of insomnia [FDA Label], [L5539]. Furthermore, such management is generally predominantly associated with the symptomatic relief of transient and short-term insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings and/or early morning awakenings [F3718]. In particular, the official prescribing information for temazepam typically specifies that the instructions issued for dispensed prescriptions of the medication should indicate specifically that patients are only expected to use the therapy for short periods of time - usually 7-10 days in general [FDA Label, F3718]. Subsequently, treatment with temazepam should usually not exceed 7 to 10 consecutive days and nor should it be prescribed in quantities exceeding a one-month supply [F3718]. Some regional prescribing information also notes that temazepam may be used for premedication prior to minor surgery or other related procedures [L5539].

METABOLISM First-pass metabolism of temazepam is minimal at approximately 5-8% of an administered dose [F3718, L5539]. Nevertheless, temazepam is principally metabolized in the liver where most of the unchanged drug is directly conjugated to glucuronide and excreted in the urine [F3718, L5539]. In particular, the primary metabolite present in the blood is the O-conjugate of temazepam [FDA Label, F3718, L5539]. Less than 5% of the drug is demethylated to oxazepam and subsequently eliminated as the glucuronide [F3718, L5539]. Regardless, the glucuronides of temazepam have no demonstrable CNS activity and it is believed that no active metabolites are formed in general [FDA Label, F3718, L5539].

ABSORPTION Studies demonstrate that between 90 to 100% of an orally administered temazepam dose is absorbed, making the medication very well absorbed [F3718, L5539]. The oral administration of 15 to 45 mg temazepam resulted in rapid absorption with significant blood levels achieved in 30 minutes and peak levels at 2-3 hours [F3718, L5539]. In particular, direct studies following the oral ingestion of 30 mg of temazepam revealed measurable plasma concentrations were obtained 10-20 minutes after dosing with peak plasma levels ranging between 666-982 ng/mL (with a mean of 865 ng/mL) presenting approximately 1.2-1.6 hours (with a mean of 1.5 hours) after the dosing [FDA Label]. Finally, a dose-proportional relationship was established for the area under the plasma concentration/time curve over the 15 to 30 mg dose range [FDA Label].

HALF-LIFE The terminal half-life determined for temazepam is recorded as being between 3.5-18 hours, with a mean of 9 hours [F3718, L5539].

MOA Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body [A175207, A175210, F3718, F3721]. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors [A175207, A175210, F3718, F3721]. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons [A175207, A175210, F3718, F3721]. ; ; Subsequently, benzodiazepines like temazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors [A175207, A175210, F3718, F3721]. This binding acts to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors [A175207, A175210, F3718, F3721]. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells [A175207, A175210, F3718, F3721]. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action [A175207, A175210, F3718, F3721].

INDICATION Temazepam is specifically indicated only for the short-term management of insomnia [FDA Label], [L5539]. Furthermore, such management is generally predominantly associated with the symptomatic relief of transient and short-term insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings and/or early morning awakenings [F3718]. In particular, the official prescribing information for temazepam typically specifies that the instructions issued for dispensed prescriptions of the medication should indicate specifically that patients are only expected to use the therapy for short periods of time - usually 7-10 days in general [FDA Label, F3718]. Subsequently, treatment with temazepam should usually not exceed 7 to 10 consecutive days and nor should it be prescribed in quantities exceeding a one-month supply [F3718].; ; Some regional prescribing information also notes that temazepam may be used for premedication prior to minor surgery or other related procedures [L5539].

DESCRIPTION Temazepam is a benzodiazepine drug, with sedative and hypnotic actions. (GtoPdb)

MOA Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body [A175207, A175210, F3718, F3721]. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors [A175207, A175210, F3718, F3721]. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons [A175207, A175210, F3718, F3721]. Subsequently, benzodiazepines like temazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors [A175207, A175210, F3718, F3721]. This binding acts to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors [A175207, A175210, F3718, F3721]. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells [A175207, A175210, F3718, F3721]. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action [A175207, A175210, F3718, F3721].

TOXICITY Manifestations of acute overdosage of temazepam, as with other benzodiazepines, can be expected to reflect the increasing CNS effects of the drug and include somnolence, confusion, and coma, with reduced or absent reflexes [FDA Label] [L5539, F3718, F3721]. With large overdoses, respiratory depression, hypotension, and finally coma can occur [FDA Label] [L5539, F3718, F3721]. Benzodiazepines like temazepam might cause fetal harm when administered to a pregnant woman. Transplacental distribution has in the past resulted in neonatal CNS depression following the ingestion of therapeutic doses of related benzodiazepine hypnotics like diazepam during the last weeks of pregnancy [FDA Label] [L5539, F3718, F3721]. It is not known whether this drug is excreted in human milk [FDA Label] [L5539, F3718, F3721]. Caution should, therefore, be exercised when temazepam is administered to a nursing woman [FDA Label] [L5539, F3718, F3721]. Safety and effectiveness in pediatric patients have not been established [FDA Label] [L5539, F3718, F3721]. Lower doses of temazepam, like 7.5 mg is recommended as the initial dosage for patients aged 65 and over since the risk of the development of oversedation, dizziness, confusion, ataxia and/or falls increases substantially with larger doses of benzodiazepines in elderly and debilitated patients [FDA Label] [L5539, F3718, F3721]. No evidence of carcinogenicity was observed in animal studies although hyperplastic liver nodules were observed in female mice exposed to the highest doses of temazepam [FDA Label] [L5539, F3718, F3721]. The clinical significance of this finding is not known [FDA Label] [L5539, F3718, F3721]. Fertility in male and female rats was not adversely affected by temazepam toxicity studies [FDA Label] [L5539, F3718, F3721]. No mutagenicity tests have been done with temazepam [FDA Label] [L5539, F3718, F3721].

TOXICITY Manifestations of acute overdosage of temazepam, as with other benzodiazepines, can be expected to reflect the increasing CNS effects of the drug and include somnolence, confusion, and coma, with reduced or absent reflexes [FDA Label] [L5539, F3718, F3721]. With large overdoses, respiratory depression, hypotension, and finally coma can occur [FDA Label] [L5539, F3718, F3721].; ; Benzodiazepines like temazepam might cause fetal harm when administered to a pregnant woman. Transplacental distribution has in the past resulted in neonatal CNS depression following the ingestion of therapeutic doses of related benzodiazepine hypnotics like diazepam during the last weeks of pregnancy [FDA Label] [L5539, F3718, F3721].; ; It is not known whether this drug is excreted in human milk [FDA Label] [L5539, F3718, F3721]. Caution should, therefore, be exercised when temazepam is administered to a nursing woman [FDA Label] [L5539, F3718, F3721].; ; Safety and effectiveness in pediatric patients have not been established [FDA Label] [L5539, F3718, F3721].; ; Lower doses of temazepam, like 7.5 mg is recommended as the initial dosage for patients aged 65 and over since the risk of the development of oversedation, dizziness, confusion, ataxia and/or falls increases substantially with larger doses of benzodiazepines in elderly and debilitated patients [FDA Label] [L5539, F3718, F3721].; ; No evidence of carcinogenicity was observed in animal studies although hyperplastic liver nodules were observed in female mice exposed to the highest doses of temazepam [FDA Label] [L5539, F3718, F3721]. The clinical significance of this finding is not known [FDA Label] [L5539, F3718, F3721].; ; Fertility in male and female rats was not adversely affected by temazepam toxicity studies [FDA Label] [L5539, F3718, F3721].; ; No mutagenicity tests have been done with temazepam [FDA Label] [L5539, F3718, F3721].

Compound Sets

Cayman Chemical Bioactives

15918

23397

15859

18565

18481

23789

ChEMBL Approved Drugs

CHEMBL967

ChEMBL Drugs

CHEMBL967

DrugBank

DB00231

DrugBank Approved Drugs

DB00231

DrugCentral

2585

DrugCentral Approved Drugs

2585

DrugMAP

DM02A65

DrugMAP Approved Drugs

DM02A65

DrugMatrix

Guide to Pharmacology

7300

NCATS Inxight Approved Drugs

I1HX8463I0

NPC Screening Collection

ReFrame library

The Spectrum Collection

Withdrawn 2.0

w231

External IDs

Properties

(calculated by RDKit )

Molecular Weight

300.07

Hydrogen Bond Acceptors

Hydrogen Bond Donors

Rotatable Bonds

Ring Count

Aromatic Ring Count

cLogP

2.47

TPSA

52.9

Fraction CSP3

0.12

Chiral centers

1.0

Largest ring

7.0

QED

0.88

Structural alerts

No structural alerts detected

Related compounds

Custom attributes

(extracted from source data)

ATC

N05CD07

Toxicity type

respiratory

Therapeutic Class

Hypnotics and Sedatives

Source data