Temazepam

Introduction to Temazepam

[​IMG]Temazepam (Restoril, Normison, Gelthix, Perdorm, Apo-Temazepam, Levanzene, Novo-Temazepam) is a strong and quick intermediate-acting benzodiazepine drug with hypnotic, sedative, anticonvulsant and anxiolytic (anti-anxiety) effects. One of the most prescribed benzodiazepines since the 1980s, temazepam is used to treat adults for insomnia. Because of the potential for abuse and the likelihood that acquired tolerance quickly requires increased doses to maintain effectiveness, temazepam is recommended as a strictly short-term treatment for insomnia. Temazepam is also used to treat anxiety, the symptoms of acute alcohol withdrawal, and muscle spasms, and is prescribed to children for night terrors and sleep walking. [1]

Like all benzodiazepines, temazepam works through enhancing the effects of GABA the main neurotransmitter that inhibits and calms the central nervous system.

In addition to its official labelled uses temazepam is used recreationally, though it has been reported to produce less euphoria than other benzodiazepines, and is also used to counteract the effects of overdose symptoms of many licit and illicit drugs, especially stimulants and psychedelics.[2]

Using Temazepam

Ways of Administration

Temazepam commonly comes in 10, 20, and 30mg tablets, to be taken orally or sub lingually.

Gel filled caplets, called 'jellies' have previously been prescribed, however, due to Temazepam users injecting the gel, this practice has been largely discontinued.

Effects of Temazepam

Temazepam is a hypnotic that promotes sleep. Sleep laboratory studies of both insomniacs and normal subjects have shown temazepam shortens sleep latency (the time it takes to fall asleep), lengthens sleeping time, and decreases the number of awakenings in a night. Normal sleep patterns are however altered by temazepam.[3]

Combinations with Temazepam

Temazepam combinations with other central nervous system depressants pose dangers because of the increased likelihood of greater respiratory depression and an increase in other effects such as lack of coordination, dizziness, low blood pressure, unconsciousness and even coma. These depressants include alcohol, other benzodiazepines, barbiturates, antipsychotics, sedative antihistamines, anticonvulsants, deliriant and dissociative drugs, muscle relaxants, opioids/opiates, sedative/hypnotics, anxiolytics, narcotic analgesics, anesthetics, MAO inhibitors, and other antidepressants.[4]

Different Uses for Temazepam

Pharmacology of Temazepam

Temazepam has an oral bioavailability of >90%. The time for temazepam to achieve peak plasma concentrations is 1-2 hours. Temazepam has a medium half-life of about 10 hours. Temazepam is a classical benzodiazepine (along with chlordiazepoxide and lorazepam) because its attributes are multi-faceted and it produces all effects that [5]

Temazepam works by activating the GABAA receptor at the benzodiazepine (BZP) site. GABA levels in the brain are not increased by temazepam, but it potentiates naturally occurring GABA by binding to a BZP located on the post synaptic receptor plate in a GABAergic nerve terminal. This is how temazepam creates sedation and its other effects. Glucuronidation by UGT, (uridine diphosphate glucuronosyltransferase.) is the primary pathway by which temazepam is metabolized into its metabolites, all of which are pharmacologically inactive. Temazepam undergoes little first-pass metabolism (about 8%), and its excretion is primarily renal.[6]

Chemistry of Temazepam


Column 1 Column 2
Systematic(IUPAC) name: 7-Chloro-1,3-dihydro-3-hydroxy-1-methyl-5-phenyl-1,4-benzodiazepin-2-one
Synonyms: 7-chloro-3-hydroxy-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 2H-1,4-benzodiazepin-2-one, 7-chloro-3-hydroxy-1-methyl-5-phenyl-2,3-dihydro-1H-benzo[f]-1,4-diazepin-2-one, 3-hydroxydiazepam, N-methyloxazepam, oxydiazepam, ER-115, K-3917, Ro-5-5345, Euhypnos, Euipnos, Gelthix, Levanxene, Levanxol, Normison, Perdorm, Planum, Remestan, Restoril, Apo-Temazepam, Levanzene, Novo-Temazepam
Molecular Formula: C16H13ClN2O2
Molar mass: 300.74 g/mol [2]
CAS Registry Number: 846-50-4
Melting Point: 119-121℃
Boiling Point: no data
Flash Point: no data
Solubility: very slightly soluble in water, sparingly soluble in alcohol
Additionnal data: none
Notes: crystallized from cyclohexane
[1]

The Dangers of Temazepam

Physical Health Risks

Perceptual and Motor function impairments

The common side effects of temazepam include drowsiness, sedation, blurring of vision, unsteadiness, and lack of coordination. These are likely to be worsened if temazepam is taken with alcohol or other depressants. [7] [8]

Rebound effects

Abrupt withdrawal of temazepam especially following excessive dosage may produce convulsions, or a condition resembling delirium tremens. [9] [10]

Overdose

Overdose of Temazepam is treated in the same manner as other benzodiazepines, with the IV administration of Flumazenil.

Reported Deaths

A study of sedative and anxiolytic poisoning deaths in New Zealand in 2001 found a single case which temazepam was the primary agent of death, and 4 further deaths in which temazepam was involved with other substances, but also found temazepam to be among the safest of sedatives with a rate of 2.1 deaths per million defined daily doses dispensed (compared to alprazolam's 16, clonazepam's 16.1, diazepam’s 5.2, lorazepam’s 1.9 and zopiclone's 0.59.[11]
An earlier 1993 British study found temazepam to have a very high number of deaths per million prescriptions (11.9) compared to other common prescription medications (11.9, versus 5.9 for benzodiazepines overall, taken with or without alcohol).[12]

Mental Health Risks

Anteriograde Amnesia

Anterograde amnesia (the inability to convert short term memories into long term memories) has been reported with benzodiazepines taken in therapeutic doses. This is a rare side-effect of temazepam but is dose-related and elderly subjects may be at particular risk. Cases of transient global amnesia have also been reported with benzodiazepine use.[13]

Abnormal Thinking, Suicidal Ideation and Psychotic Behaviour

Temazepam use has a (very small) risk of abnormal thinking, thoughts of suicide and psychotic behavior. These may be characterized by decreased inhibition, for example in aggression or extroversion that seem excessive, as occurs with alcohol use. A history of violence or unusual reactions to sedatives seems associated with a greater risk of these rare effects and other bizarre behavior, hallucinations, and depersonalization. Such behaviors have been reported more with high doses and chronic use of benzodiazepines but also happen during acute, maintenance or withdrawal phases of benzodiazepine treatment. These are potentially very serious, temazepam should be stopped and immediate medical assistance sought.[14]

Rebound Insomnia and Anxiety

Rebound insomnia and rebound anxiety can be caused when temazepam is stopped too abruptly, especially if the use has been long term and/or at higher than normal therapeutic doses. Temazepam use should be tapered gradually as symptoms such as depression, nervousness, rebound insomnia, and irritability are reported when temazepam is suddenly stopped in patients receiving even normal therapeutic doses for short periods of time. [15]

Side Effects

Like many medications, temazepam can cause allergic, reaction, but this is uncommon. Symptoms of an allergic reaction may include swelling of lips, throat, tongue and face, trouble breathing and hives. If this occurs medical help must be sought immediately since allergic reactions progress very quickly and they can be fatal, though death is a very unusual outcome.
In rare cases patients have reported experiencing the following as side effects of temazepam: low blood pressure, gastrointestinal and visual disturbances, skin rashes, urinary retention, headache, vertigo, changes in sex-drive, blood abnormalities, and jaundice.

Addiction

Physical Addiction

Physical dependence and addiction to temazepam are possible even when it is taken for short periods at therapeutic doses. Higher doses and longer periods of use increase this risk of addiction. Abruptly stopping temazepam especially after long-term use and/or higher doses can cause serious benzodiazepine withdrawal syndrome. But withdrawal symptoms including seizure have been reported even after only short therapy on doses of at therapeutic levels. There is overlap between benzodiazepine withdrawal symptoms and those of anxiety and panic; others including hypersensitivity to sensory stimuli, depersonalisation, and derealisation, abnormal perception of movement, appetite and weight loss, depressed mood, epileptic seizures and other neuropsychiatric symptoms and schizophreniform features. Many of the symptoms of benzodiazepine withdrawal are those experienced by people undergoing withdrawal from barbiturates and alcohol. However, the severity of these symptoms does seem connected to length of treatment and dose levels, and it has been reported that these are more severe when doses are decreased quickly or discontinued without tapering.

A case of catatonia resulting from temazepam has been reported in an elderly woman who had been taking 40mg/day for 40 years. [16]

Mental Addiction

In general the dependence potential of temazepam is low but increases when it is taken for longer periods, at higher doses and by patients with a history of drug abuse, addiction or alcoholism or patients with marked personality disorders. [17]

Producing/Growing Temazepam

Forms of Temazepam

Temazepam is typically taken orally and comes in capsules of 15mg.

Legal Status of Temazepam


Temazepam is a controlled substance 21 CFR 1308.14

United Nations

USA

Australia

Temazepam is a Schedule 4 [Appendix D] substance and is only available with a prescription.
It is subject to additonal prescribing requirements over regular Schedule 4 substances due to its addictive nature.

EU

Other Countries

History of Temazepam

More Temazepam Sections


Temazepam



References

  1. ^
  2. ^
  3. ^Restoril (temazepam) monograph, Mallinkrodt, revised 2010.
  4. ^Restoril (temazepam) monograph, Mallinkrodt, revised 2010.
  5. ^Restoril (temazepam) monograph, Mallinkrodt, revised 2010.
  6. ^Restoril (temazepam) monograph, Mallinkrodt, revised 2010.
  7. ^Liljequist, R.; Mattila, M. J. (1979). "Acute effects of temazepam and nitrazepam on psychomotor skills and memory". Acta Pharmacologica et Toxicologica 44 (5): 364–369.
  8. ^ Tedeschi G, Griffiths AN, Smith AT, Richens A (1985). The effect of repeated doses of temazepam and nitrazepam on human psychomotor performance. Br J Clin Pharmacol 20 (4): 361–7.
  9. ^ MacKinnon GL; Parker WA (1982). Benzodiazepine withdrawal syndrome: a literature review and evaluation. The American journal of drug and alcohol abuse 9 (1): 19–33.
  10. ^Kales A, Bixler EO, Soldatos CR, Vela-Bueno A, Jacoby JA, Kales JD (March 1986). Quazepam and temazepam: effects of short- and intermediate-term use and withdrawal . Clin. Pharmacol. Ther. 39 (3): 345–52.
  11. ^David M. Reith, John Fountain, Rebecca McDowell, and Murray Tilyard (2003) Comparison of the Fatal Toxicity Index of Zopiclone with Benzodiazepines. Journal of Toxicology: Clinical Toxicology 41(7): 975–980.
  12. ^Serfaty M, Masterton G (1993). Fatal poisonings attributed to benzodiazepines in Britain during the 1980s. Br J Psychiatry 163: 386–93.
  13. ^Restoril (temazepam) monograph, Mallinkrodt, revised 2010.
  14. ^Restoril (temazepam) monograph, Mallinkrodt, revised 2010.
  15. ^Kales A, Bixler EO, Soldatos CR, Vela-Bueno A, Jacoby JA, Kales JD (March 1986). Quazepam and temazepam: effects of short- and intermediate-term use and withdrawal. Clin. Pharmacol. Ther. 39 (3): 345–52.
  16. ^Parameswaran, Ram ; Moore, Katherine ; Hannan, Terry ; Austin, Marni
    (2011). Catatonia associated with temazepam withdrawal. The Australian and New Zealand journal of psychiatry 45(11):1006-7.
  17. ^Kales A, Bixler EO, Soldatos CR, Vela-Bueno A, Jacoby JA, Kales JD (1986). Quazepam and temazepam: effects of short- and intermediate-term use and withdrawal. Clin. Pharmacol. Ther. 39 (3): 345–52.

[1]Merck Index, fifteenth edition (2013)
[2]Calculated from Atomic Weights of the Elements, 2007

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