Loprazolam

From Wikipedia, the free encyclopedia

You have new messages (last change).
Loprazolam
Systematic (IUPAC) name
(2Z)-6-(2-Chlorophenyl)-
2-[(4-methyl-1-piperazinyl)methylene]-
8-nitro-2,4-dihydro-1H-imidazo[1,2-a]
[1,4]benzodiazepin-1-one
Identifiers
CAS number 61197-73-7
ATC code N05CD11
PubChem 3033860
DrugBank none
Chemical data
Formula C23H21ClN6O3 
Mol. mass 464.904 g/mol
Pharmacokinetic data
Bioavailability  ?
Metabolism Hepatic
Half life 6-12 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

D
Legal status

Schedule IV(US)
Routes Oral

Loprazolam marketed under the band names Dormonoct®, Havlane®, Sonin®, Somnovit®, is a drug which is an imidazole benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It is available in 1mg tablets. It is licensed and marketed for the short term treatment of severe insomnia.

Contents

[edit] Dose

The dose of Loprazolam for insomnia is usually 1 mg but can be increased to 2 mg if necessary. In the elderly a lower dose is recommended due to more pronounced effects and a significant impairment of standing up to 11 hours after dosing of 1 mg of loprazolam. The half life is much more prolonged in the elderly than in younger patients. A half life of 19.8 hours has been reported in elderly patients.[1] Patients and prescribing physicians should however bare in mind that higher doses of loprazolam may impair long term memory functions.[2]

[edit] Mechanism of Action

Loprazolam is a benzodiazepine, which acts via positively modulating the GABAa receptor complex via a binding to the benzodiazepine receptor which is situated on alpha subunit containing GABAa receptors. This action enhances the effect of the neurotransmitor GABA on the GABAa receptor complex by increasing the opening frequency of the chloride ion channel. This action allows more chloride ions to enter the neuron which in turn produces the following properties: muscle relaxation, anxiolytic, hypnotic, amnesic and anticonvulsant. These properties can be used for therapeutic benefit in clinical practise. These properties are also sometimes used for recreational purposes in the form of drug abuse of benzodiazepines where high doses are used to achieve intoxication and or sedation.[3] [4]

[edit] Pharmacokinetics

After oral administration of loprazolam on an empty stomach it takes 2 hours for serum concentration levels to reach there peak which is significantly less than other benzodiazepine hypnotics. The delay in the time for peak plasma levels to reach their maximum brings into question the benefit of loprazolam for the treatment of insomnia when compared to other hypnotics, although studies have shown that the sleep inducing properties of loprazolam occur within 0.5 hours, which may indicate rapid penetration into the brain and thus the peak plasma delay of loprazolam may not be sigificantly relevant to loprazolams benefit as a hypnotic agent for the treatment of insomnia. If loprazolam is taken after a meal the time for plasma levels to reach their peak may be delayed even further. Loprazolam induces significant changes in the electrical activity of the brain as measured by an EEG, these changes are more pronounced, the higher the dosage. Metabolism of loprazolam in humans produces an active metabolite which is similar in potency to loprazolam, in levels of about half that of parent compound, the other half is excreted unchanged as loprazolam. The half life of the active metabolite is about the same as the parent compound loprazolam.[5]

[edit] Side Effects

Side effects of loprazolam are generally the same as for other benzodiazepines such as diazepam Valium.[6] The only main difference in side effects of loprazolam and diazepam is it is less prone to day time sedation as the half life of loprazolam is considered to be intermediate whereas diazepam has a very long half life. The side effects of loprazolam are the following:

List of Side Effects

[edit] Tolerance, Dependence and Withdrawal

Loprazolam as with all other benzodiazepines is recommended for only short term management of insomnia in the UK due to the serious concerns of adverse affects of long term usage of benzodiazepines such as tolerance, dependency and withdrawal phenomenom as well as adverse effects on mood and cognition. Prolonged usage of benzodiazepines also is not recommended due to a lack of efficacy in there therapeutic actions due to tolerance to their effects and concerns of increasing physical and psychological adverse effects of some patients on long term benzodiazepines, eg agorophobia, gastrointestinal and peripheral nerve abnormalities such as burning and tingling sensations.[7] [8]

Loprazolam however has a low risk of dependence (addiction) and withdrawal phenomenom if it is used for less than 4 weeks or very occasionally. However in one placebo controlled study comparing 3 week treatment for insomnia of either loprazolam or triazolam rebound anxiety and insomnia occured 3 days after discontinuing loprazolam therapy whereas with triazolam the rebound anxiety and insomnia was seen the next day. The difference between the two benzodiazepines in time for rebound or withdrawal phenomenom to appear is likely due to the difference in the elimination half life of the two drugs.[9] [10] These results would suggest that loprazolam and possibly other benzodiazepines should be prescribed for 1 - 2 weeks rather than 2 - 4 weeks to reduce the risk of physical dependence or and withdrawal or rebound phenomenom.

Withdrawal Symptoms

It should be noted that slow reduction of the dosage over a period of months at a rate which the individual can tolerate greatly minimises the severity of the withdrawal symptoms. It is usually recommended for individuals dependent on benzodiazepines cross to an equivalent dose of diazepam to gradually taper as diazepam has a longer half life and small dose reductions can be achieved compared to other benzodiazepines. [11] [12]

Major complications can occur after abrupt or over rapid withdrawal especially from high doses producing symptoms such as:

It has been estimated that between 30% and 50% of long term users of benzodiazepines will experience withdrawal symptoms. [13] However up to 90% of patients withdrawing from benzodiazepines experienced withdrawal symptoms in one study, however the rate of taper was very fast at 25% of dose per week. [14] Withdrawal symptoms tend to last between 3 weeks to 3 months, although 10 - 15% of people may experience a protracted withdrawal syndrome with symptoms persisting and gradually declining over a period of many months and occasional several years.[15]

[edit] References

  1. ^ Swift CG, Swift MR, Ankier SI, Pidgen A, Robinson J. (1985). Single dose pharmacokinetics and pharmacodynamics of oral loprazolam in the elderly.. British journal of clinical pharmacology. Retrieved on 2007-03-21.
  2. ^ Bareggi SR, Ferini-Strambi L, Pirola R, Franceschi M, Smirne S. (1991). Effects of loprazolam on cognitive functions.. Psychopharmacology (Berl).. Retrieved on 2007-03-21.
  3. ^ Bateson AN (2002). Basic pharmacologic mechanisms involved in benzodiazepine tolerance and withdrawal.. ingentaconnect. Retrieved on 2007-03-21.
  4. ^ Professor C Heather Ashton (2002). BENZODIAZEPINE ABUSE. Harwood Academic. Retrieved on 2007-03-22.
  5. ^ Mamelak M, Bunting P, Galin H, Price V, Csima A, Young T, Klein D, Pelchat JR. (1988). Serum and quantitative electroencephalographic pharmacokinetics of loprazolam in the elderly.. Journal of clinical pharmacology. Retrieved on 2007-03-21.
  6. ^ British National Formulary Benzodiazepines Information
  7. ^ Committee on Safety of Medicines (1988). BENZODIAZEPINES, DEPENDENCE AND WITHDRAWAL SYMPTOMS. Medicines Control Agency UK Government. Retrieved on 2007-03-21.
  8. ^ Professor C Heather Ashton (1987). Benzodiazepine Withdrawal: Outcome in 50 Patients. benzo. Retrieved on 2007-03-21.
  9. ^ Morgan K, Oswald I (1982). Anxiety caused by a short-life hypnotic. British medical journal (Clinical research ed.). Retrieved on 2007-03-21.
  10. ^ Morgan K, Adam K, Oswald I (1984). Effect of loprazolam and of triazolam on psychological functions.. Psychopharmacology. Retrieved on 2007-03-21.
  11. ^ Ashton CH (2001). REASONS FOR A DIAZEPAM (VALIUM) TAPER. BCNC. Retrieved on 2007-03-21.
  12. ^ (Roche Products (UK) Ltd 1990) Benzodiazepines and Your Patients: A Management Programme
  13. ^ Ashton CH (1985). BENZODIAZEPINE DEPENDENCE AND WITHDRAWAL: AN UPDATE. benzo org uk. Retrieved on 2007-03-21.
  14. ^ Schweizer E, Rickels K, Case WG, Greenblatt DJ. (1990). Long-term therapeutic use of benzodiazepines. II. Effects of gradual taper.. Arch Gen Psychiatry. Retrieved on 2007-03-21.
  15. ^ Ashton CH (2002). BENZODIAZEPINES: How They Work and How to Withdraw. benzo org uk. Retrieved on 2007-03-21.

[edit] External links

v • d • e
Benzodiazepines

Adinazolam, Alprazolam, Bentazepam, Bromazepam, Brotizolam, Camazepam, Chlordiazepoxide, Cinolazepam, Clobazam, Clonazepam, Clorazepate, Clotiazepam, Cloxazolam, Cyprazepam, Diazepam, Doxefazepam, Estazolam, Ethyl loflazepate, Etizolam, Fludiazepam, Flunitrazepam, Flurazepam, Flutazolam, Flutoprazepam, Gidazepam, Halazepam, Haloxazolam, Ketazolam, Loprazolam, Lorazepam, Lormetazepam, Medazepam, Mexazolam, Midazolam, Nimetazepam, Nitrazepam, Nordazepam, Oxazepam, Oxazolam, Phenazepam, Pinazepam, Prazepam, Quazepam, Temazepam, Tetrazepam, Tofisopam, Triazolam, Zolazepam


Pills  This pharmacology-related article is a stub. You can help Wikipedia by expanding it.
Retrieved from "http://en.wikipedia.org../../../l/o/p/Loprazolam.html"
In other languages