Quazepam

From Self-sufficiency
Jump to: navigation, search
Quazepam
150px
150px
Systematic (IUPAC) name
7-chloro- 5-(2-fluorophenyl)- 1-(2,2,2-trifluoroethyl)- 1,3-dihydro- 2H -1,4-benzodiazepin- 2-thione
Clinical data
Pregnancy
category
  • AU: X (High risk)
  • US: X (Contraindicated)
Routes of
administration		 Oral
Legal status
Legal status
Pharmacokinetic data
Bioavailability 29–35%
Metabolism Hepatic
Biological half-life 39 hours
Excretion Renal
Identifiers
CAS Number 36735-22-5
ATC code N05CD10 (WHO)
PubChem CID 4999
DrugBank DB01589
Chemical data
Formula C17H11ClF4N2S
Molar mass 386.795 g/mol[[Script error: No such module "String".]]
  (verify)
Script error: No such module "TemplatePar".Expression error: Unexpected < operator.

Quazepam (marketed under brand names Doral, Dormalin) is a drug which is a benzodiazepine derivative. Quazepam is indicated for the treatment of insomnia including sleep induction and sleep maintenance.[1] Quazepam induces impairment of motor function and has hypnotic and anticonvulsant properties with less overdose potential than other benzodiazepines.[2][3] Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.[4] Quazepam is a trifluoroethyl type of benzodiazepine. Quazepam is unique amongst benzodiazepines in that it selectively targets the GABAA type1 receptors which are responsible for inducing sleep. Its mechanism of action is very similar to zolpidem and zaleplon in its pharmacology and can successfully substitute for zolpidem and zaleplon in animal studies.[5][6][7] Quazepam is manufactured by the pharmaceutical corporation Schering-Plough.[8]

Indications

Quazepam is used for short term treatment of insomnia related to sleep induction or sleep maintenance problems and has demonstrated superiority over other benzodiazepines such as temazepam.[9][10][11][12] Usual dosage is 7.5 to 15 mg orally at bedtime.[13]

Quazepam is effective as a premedication prior to surgery.[14]

Side effects

Quazepam has fewer side effects than other benzodiazepines and less potential to induce tolerance and rebound effects.[15][16] There is significantly less potential for quazepam to induce respiratory depression or to adversely effect motor coordination than other benzodiazepines.[17] The different side effect profile of quazepam may be due to its more selective binding profile to type1 benzodiazepine receptors.[18][19]

Tolerance and dependence

Tolerance may occur to quazepam but more slowly than seen with other benzodiazepines such as triazolam.[24] However, quazepam causes significantly less drug tolerance and less withdrawal symptoms including less rebound insomnia upon discontinuation compared to other benzodiazepines.[25][26][27][28] Quazepam may cause less rebound effects than other type1 benzodiazepine receptor selective nonbenzodiazepine drugs due to its longer half life.[29] Short acting hypnotics often cause next day rebound anxiety. Quazepam due to its pharmacological profile does not cause next day rebound withdrawal effects during treatment.[30]

No firm conclusions can be drawn however, whether long term use of quazepam does not produce tolerance as few if any long term clinical trials extending beyond 4 weeks of chronic use have been conducted.[31] Quazepam should be withdrawn gradually if used beyond 4 weeks of use to avoid the risk of a severe benzodiazepine withdrawal syndrome developing. Very high dosage administration over prolonged periods of time, up to 52 weeks, of quazepam in animal studies provoked severe withdrawal symptoms upon abrupt discontinuation, including excitability, hyperactivity, convulsions and the death of two of the monkeys due to withdrawal related convulsions. More monkeys died however, in the diazepam treated monkeys.[32] In addition it has now been documented in the medical literature that one of the major metabolites of quazepam, N-desalkyl-2-oxoquazepam (N-desalkylflurazepam), which is long acting and prone to accumulation, binds unselectively to benzodiazepine receptors, thus quazepam may not differ all that much pharmacologically from other benzodiazepines.[33]

Special precautions

Benzodiazepines require special precaution if used in the during pregnancy, in children, alcohol or drug-dependent individuals and individuals with comorbid psychiatric disorders.[34]

Caution in breast feeding. Quazepam and its active metabolites are excreted into breast milk.[35]

Caution elderly. Accumulation of one of the active metabolites of quazepam, N-desalkyl-2-oxoquazepam (N-desalkylflurazepam), may occur in the elderly. A lower dose may be required in the elderly.[36]

Elderly

Quazepam is more tolerable for elderly patients compared to flurazepam due to its reduced next day impairments.[37] However, another study showed marked next day impairments after repeated administration due to accumulation of quazepam and its long acting metabolites. Thus the medical literature shows conflicts on quazepam's side effect profile.[38] A further study showed significant balance impairments combined with an unstable posture after administration of quazepam in test subjects.[39] An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including quazepam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.[40]

Pharmacology

Quazepam is selective for type I benzodiazepine receptors containing the alpha1 subunit, similar to other drugs such as zaleplon and zolpidem. As a result quazepam has little or no muscle relaxant properties. Most other benzodiazepines are unselective and bind to type1 GABAA receptors and type2 GABAA receptors. Type1 GABAA receptors include the alpha1 subunit containing GABAA receptors which are responsible for hypnotic properties of the drug. Type2 receptors include the alpha2, alpha3 and alpha5 subunits which are responsible for anxiolytic, amnesia and muscle relaxant properties.[41][42] Thus quazepam may have less side effects than other benzodiazepines but, it has a very long half life of 25 hours which reduces its benefits as a hypnotic due to likely next day sedation. It also has two active metabolites with half lives of 28 and 79 hours. Quazepam may also cause less drug tolerance than other benzodiazepines such as temazepam and triazolam perhaps due to its subtype selectivity.[43][44][45][46] The longer half life of quazepam may have the advantage however, of causing less rebound insomnia than shorter acting subtype selective nonbenzodiazepines.[47][48] However, one of the major metabolites of quazepam, the N-desmethyl-2-oxoquazepam (aka N-desalkyflurazepam), binds unselectively to both type1 and type2 GABAA receptors. The N-desmethyl-2-oxoquazepam metabolite also has a very long half life and likely contributes to the pharmacological effects of quazepam.[49]

Pharmacokinetics

Quazepam has an absorption half life of 0.4 hours with a peak in plasma levels after 1.75 hours. It is eliminated both renally and through feces.[50] The active metabolites of quazepam are 2-oxoquazepam and N-desalkyl-2-oxoquazepam. The N-desalkyl-2-oxoquazepam metabolite has only limited pharmacological activity compared to the parent compound quazepam and the active metabolite 2-oxoquazepam. Quazepam and its major active metabolite 2-oxoquazepam both show high selectivity for the type1 GABAA receptors.[51][52][53][54] The elimination half life range of quazepam is between 27 to 41 hours.[31]

Interactions

The absorption rate is likely to be significantly reduced if quazepam is taken in the fasted state reducing the hypnotic effect of quazepam.If 3 or more hours have passed since eating food then some food should be eaten before taking quazepam.[55][56]

Mechanism of action

Quazepam modulates specific GABAA receptors via the benzodiazepine site on the GABAA receptor. This modulation enhances the actions of GABA, causing an increase in opening frequency of the chloride ion channel which results in an increased influx of chloride ions into the GABAA receptors. Quazepam, unique amongst benzodiazepine drugs selectively targets type1 benzodiazepine receptors which results reduced sleep latency in promotion of sleep.[57][58][59] Quazepam also has some anticonvulsant properties.[60]

EEG and sleep

Quazepam has potent sleep inducing and sleep maintaining properties.[61][62] Studies in both animals and humans have demonstrated that EEG changes induced by quazepam resemble normal sleep patterns whereas other benzodiazepines disrupt normal sleep. Quazepam promotes slow wave sleep.[63][64] This positive effect of quazepam on sleep architecture may be due to its high selectivity for type1 benzodiazepine receptors as demonstrated in animal and human studies. This makes quazepam unique in the benzodiazepine family of drugs.[65][66]

Drug misuse

See also: Benzodiazepine drug misuse

Quazepam is a drug with the potential for misuse. Two types of drug misuse can occur either recreational misuse is where the drug is taken to achieve a high or when the drug is continued long term against medical advice.[67]

See also

References

Cite error: Invalid <references> tag; parameter "group" is allowed only.

Use <references />, or <references group="..." />

External links

Benzodiazepine derivatives (N05BA, N05CD)
1,4-Benzodiazepines

Bromazepam · Camazepam · Carburazepam · Chlordiazepoxide · Cinolazepam · Clonazepam · Clorazepate · Cyprazepam · Delorazepam · Demoxepam · Devazepide* · Diazepam · Doxefazepam · Elfazepam · Ethyl carfluzepate · Ethyl dirazepate · Ethyl loflazepate · Fletazepam · Fludiazepam · Flunitrazepam · Flurazepam · Flutemazepam · Flutoprazepam · Fosazepam · Gidazepam · Halazepam · Iclazepam · Ketazolam · Lorazepam · Lormetazepam · Meclonazepam · Medazepam · Menitrazepam · Metaclazepam · Motrazepam · Nimetazepam · Nitrazepam · Nitrazepate · Nordazepam · Nortetrazepam · Oxazepam · Phenazepam · Pinazepam · Pivoxazepam · Prazepam · Proflazepam · Quazepam · QH-II-66 · Reclazepam · Ro5-2904 · Sulazepam · Temazepam · Tetrazepam · Tifluadom* · Tolufazepam · Tuclazepam · Uldazepam

1,5-Benzodiazepines
2,3-Benzodiazepines *
Triazolobenzodiazepines
Imidazobenzodiazepines
Oxazolobenzodiazepines
Thienodiazepines
Pyridodiazepines
Pyrazolodiazepines
Pyrrolodiazepines
Tetrahydroisoquinobenzodiazepines
Benzodiazepine prodrugs
 * atypical activity profile (not GABAA receptor ligands)
GABAA receptor
Ultrashort-acting
Short/intermediate-
acting
Long-acting
Ungrouped
Short-acting
Intermediate-acting
Long-acting
Flurazepam • Flutoprazepam • Nitrazepam • Quazepam
Dialkylphenols
Alpha-2 adrenergic
receptor
Melatonin receptor
Histamine receptor &
Acetylcholine receptor
5-HT2A &
α1-adrenergic
Selective 5-HT2A & α1-adrenergic antagonists
GABAB receptor /
GHB receptor
GHB Type
Orexin receptors
Orexin antagonists
Other receptors/
ungrouped
Other

M: PSO/PSI

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc, drug(N5A/5B/5C/6A/6B/6D)

ja:クアゼパム
  1. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  2. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  3. ↑ Ongini E, Parravicini L, Bamonte F, Guzzon V, Iorio LC, Barnett A (1982). "Pharmacological studies with quazepam, a new benzodiazepine hypnotic". Arzneimittelforschung. 32 (11): 1456–62. PMID 6129857. 
  4. ↑ Roth T, Tietz EI, Kramer M, Kaffeman M (1979). "The effect of a single dose of quazepam (Sch-16134) on the sleep of chronic insomniacs". J. Int. Med. Res. 7 (6): 583–7. PMID 42593. 
  5. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  6. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  7. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  8. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  9. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  10. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  11. ↑ Hernández Lara R, Del Rosal PL, Ponce MC (1983). "Short-term study of quazepam 15 milligrams in the treatment of insomnia". J. Int. Med. Res. 11 (3): 162–6. PMID 6347748. 
  12. ↑ Caldwell JR (1982). "Short-term quazepam treatment of insomnia in geriatric patients". Pharmatherapeutica. 3 (4): 278–82. PMID 6128741. 
  13. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  14. ↑ Nishiyama T, Yamashita K, Yokoyama T, Imoto A, Manabe M (2007). "Effects of quazepam as a preoperative night hypnotic: comparison with brotizolam" (PDF). J Anesth. 21 (1): 7–12. doi:10.1007/s00540-006-0445-2. PMID 17285406. 
  15. ↑ Barnett A, Iorio LC, Ongini E (1982). "The sedative-hypnotic properties of quazepam, a new hypnotic agent". Arzneimittelforschung. 32 (11): 1452–6. PMID 6129856. 
  16. ↑ Lader M (1992). "Rebound insomnia and newer hypnotics". Psychopharmacology (Berl.). 108 (3): 248–55. doi:10.1007/BF02245108. PMID 1523276. 
  17. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  18. ↑ Billard W, Crosby G, Iorio L, Chipkin R, Barnett A (1988). "Selective affinity of the benzodiazepines quazepam and 2-oxo-quazepam for BZ1 binding site and demonstration of 3H-2-oxo-quazepam as a BZ1 selective radioligand". Life Sci. 42 (2): 179–87. doi:10.1016/0024-3205(88)90681-9. PMID 2892106. 
  19. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  20. ↑ Martinez HT, Serna CT (1982). "Short-term treatment with quazepam of insomnia in geriatric patients". Clin Ther. 5 (2): 174–8. PMID 6130842. 
  21. ↑ Mendels J, Stern S (1983). "Evaluation of the short-term treatment of insomnia in out-patients with 15 milligrams of quazepam". J. Int. Med. Res. 11 (3): 155–61. PMID 6347747. 
  22. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  23. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  24. ↑ Saletu B, Anderer P, Brandstätter N; et al. (1994). "Insomnia in generalized anxiety disorder: polysomnographic, psychometric and clinical investigations before, during and after therapy with a long- versus a short-half-life benzodiazepine (quazepam versus triazolam)". Neuropsychobiology. 29 (2): 69–90. doi:10.1159/000119067. PMID 8170529. 
  25. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  26. ↑ Mamelak M, Csima A, Price V (1984). "A comparative 25-night sleep laboratory study on the effects of quazepam and triazolam on chronic insomniacs". J Clin Pharmacol. 24 (2-3): 65–75. PMID 6143767. 
  27. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  28. ↑ Altamura AC, Colacurcio F, Mauri MC; et al. (1989). "[Controlled clinical study on the effect of quazepam versus triazolam in patients with sleep disorders]". Minerva Psichiatr (in Italian). 30 (3): 159–64. PMID 2691808. 
  29. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  30. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  31. ↑ 31.0 31.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  32. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  33. ↑ Nikaido AM, Ellinwood EH (1987). "Comparison of the effects of quazepam and triazolam on cognitive-neuromotor performance". Psychopharmacology (Berl.). 92 (4): 459–64. PMID 2888152. 
  34. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  35. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  36. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  37. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  38. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  39. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  40. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  41. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  42. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  43. ↑ Jochemsen R, Breimer DD (1984). "Pharmacokinetics of benzodiazepines: metabolic pathways and plasma level profiles". Curr Med Res Opin. 8 Suppl 4: 60–79. PMID 6144464. 
  44. ↑ Kales A (1990). "Quazepam: hypnotic efficacy and side effects". Pharmacotherapy. 10 (1): 1–10; discussion 10–2. PMID 1969151. 
  45. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  46. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  47. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  48. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  49. ↑ Wang JS, DeVane CL (2003). "Pharmacokinetics and drug interactions of the sedative hypnotics" (PDF). Psychopharmacol Bull. 37 (1): 10–29. PMID 14561946. 
  50. ↑ Zampaglione N, Hilbert JM, Ning J, Chung M, Gural R, Symchowicz S (1985). "Disposition and metabolic fate of 14C-quazepam in man". Drug Metab. Dispos. 13 (1): 25–9. PMID 2858372. 
  51. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  52. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  53. ↑ Corda MG, Giorgi O, Longoni B, Ongini E, Montaldo S, Biggio G (1988). "Preferential affinity of 3H-2-oxo-quazepam for type I benzodiazepine recognition sites in the human brain". Life Sci. 42 (2): 189–97. doi:10.1016/0024-3205(88)90682-0. PMID 2892107. 
  54. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  55. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  56. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  57. ↑ Meldrum BS, Chapman AG (1986). "Benzodiazepine receptors and their relationship to the treatment of epilepsy". Epilepsia. 27 Suppl 1: S3–13. PMID 3017690. 
  58. ↑ Corda MG, Giorgi O, Longoni BM; et al. (1988). "Characterization of 3H-2-oxo-quazepam binding in the human brain". Prog. Neuropsychopharmacol. Biol. Psychiatry. 12 (5): 701–12. doi:10.1016/0278-5846(88)90015-2. PMID 2906158. 
  59. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  60. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  61. ↑ Mauri MC, Gianetti S, Pugnetti L, Altamura AC (1993). "Quazepam versus triazolam in patients with sleep disorders: a double-blind study". Int J Clin Pharmacol Res. 13 (3): 173–7. PMID 7901174. 
  62. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  63. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  64. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  65. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  66. ↑ Wamsley JK, Golden JS, Yamamura HI, Barnett A (1985). "Quazepam, a sedative-hypnotic selective for the benzodiazepine type 1 receptor: autoradiographic localization in rat and human brain". Clin Neuropharmacol. 8 Suppl 1: S26–40. PMID 2874881. 
  67. ↑ Griffiths RR, Johnson MW (2005). "Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds". J Clin Psychiatry. 66 Suppl 9: 31–41. PMID 16336040. 
Retrieved from "http://ssf.f15ijp.com/wiki/index.php?title=Quazepam&oldid=24677"