Delorazepam

Delorazepam

Systematic (IUPAC) name
7-Chloro-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2(2H)-one
Clinical data
Pregnancy cat.	?
Legal status	?
Routes	Oral
Pharmacokinetic data
Bioavailability	87%
Metabolism	Hepatic
Half-life	[60-140]
Excretion	Renal
Identifiers
CAS number	2894-67-9
ATC code	None
PubChem	CID 17925
DrugBank	DB01511
ChemSpider	16929 Y
UNII	O91W32476G Y
KEGG	D07784 Y
ChEMBL	CHEMBL268254 Y
Chemical data
Formula	C15H10Cl2N2O
Mol. mass	304.02
SMILES	eMolecules & PubChem
InChI InChI=1S/C15H10Cl2N2O/c16-9-5-6-13-11(7-9)15(18-8-14(20)19-13)10-3-1-2-4-12(10)17/h1-7H,8H2,(H,19,20) Y Key:CHIFCDOIPRCHCF-UHFFFAOYSA-N Y
Y(what is this?)  (verify)

Delorazepam also known as chlordesmethyldiazepam is a drug which is a benzodiazepine and a derivative of desmethyldiazepam.^[1] It is marketed in Italy, where it is available under the trade name EN and Dadumir.^[2] Delorazepam (chlordesmethyldiazepam) is also an active metabolite of the benzodiazepine drug cloxazolam.^[3] Adverse effects may include hangover type effects, drowsiness, behavioural impairments^[4][5] and short-term memory impairments.^[6] Similar to other benzodiazepines delorazepam has anxiolytic,^[7] skeletal muscle relaxant,^[8] hypnotic^[4] and anticonvulsant properties.^[9]

Indications

Delorazepam is mainly used as an anxiolytic because of its long elimination half-life; showing superiority over the short-acting drug lorazepam.^[10] In comparison with the antidepressant drugs, paroxetine and imipramine, delorazepam was found to be more effective in the short-term but after 4 weeks the antidepressants showed superior anti-anxiety effects.^[11]

Delorazepam is also used as a premedication for dental phobia for its anxiolytic properties.^[12]

Delorazepam has also demonstrated effectiveness in treating alcohol withdrawal.^[13]

Availability

Delorazepam is available in tablet and liquid drop formulations. The liquid drop formulation is absorbed more quickly and has improved bioavailibility.^[14]

Pharmacology

Delorazepam is well absorbed after administration, reaching peak plasma levels within 1 – 2 hours. It has a very long elimination half-life and can still be detected 72 hours after dosing.^[15] Bioavailability is about 77 percent. Peak plasma levels occur at just over one hour after administration. Significant accumulation occurs of delorazepam due to its slow metabolism; the elderly metabolise delorazepam and its active metabolite slower than younger individuals. The elderly also have a poorer response to the therapeutic effects and a higher rate of adverse effects. The elimination half-life of delorazepam is 80–115 hours. The active metabolite of delorazepam is lorazepam and represents about 15 - 24 percent of the parent drug (delorazepam).^[14][16][17] The pharmacokinetics of delorazepam are not altered if it is taken with food, except for some slowing of absorption.^[18] The potency of delorazepam is 1 mg delorazepam equals 10 mg diazepam.

Side effects and contraindications

Special cautions

People with renal failure on haemodialysis have a slow elimination rate and a reduced volume of distribution of the drug.^[19] Liver disease has a profound effect on the elimination rate of delorazepam, resulting in the half-life almost doubling to 395 hours, where as healthy patients showed an elimination half-life of 204 hours on average. Caution is recommended when using delorazepam in in patients with liver disease.^[20]

See also

• Benzodiazepine

References

1. ^ Govoni, S.; Fresia, P.; Spano, PF.; Trabucchi, M. (Nov 1976). "Effect of desmethyldiazepam and chlordesmethyldiazepam on 3',5'-cyclic guanosine monophosphate levels in rat cerebellum.". Psychopharmacology (Berl) 50 (3): 241–4. doi:10.1007/BF00426839. PMID 188062. 
2. ^ "Benzodiazepine Names". non-benzodiazepines.org.uk. http://www.non-benzodiazepines.org.uk/benzodiazepine-names.html. Retrieved 2008-12-29. 
3. ^ Oliveira-Silva, D.; Oliveira, CH.; Mendes, GD.; Galvinas, PA.; Barrientos-Astigarraga, RE.; De Nucci, G. (Dec 2009). "Quantification of chlordesmethyldiazepam by liquid chromatography-tandem mass spectrometry: application to a cloxazolam bioequivalence study.". Biomed Chromatogr 23 (12): 1266–75. doi:10.1002/bmc.1249. PMID 19488979. 
4. ^ ^{a b} Zimmermann-Tansella, C.; Tansella, M.; Lader, M. (Oct 1976). "The effects of chlordesmethyldiazepam on behavioral performance and subjective judgment in normal subjects.". J Clin Pharmacol 16 (10 Pt 1): 481–88. PMID 977791. 
5. ^ Cesco, G.; Giannico, S.; Fabbruci, I.; Scaggiante, L.; Montanaro, N. (1977). "Single-blind evaluation of hypnotic activity of chlordesmethyldiazepam in No-placebo-reactor medical patients.". Arzneimittelforschung 27 (1): 146–8. PMID 322671. 
6. ^ Scarone, S.; Strambi, LF.; Cazzullo, CL. (1981). "Effects of two dosages of chlordesmethyldiazepam on mnestic-information processes in normal subjects.". Clin Ther 4 (3): 184–91. PMID 6796270. 
7. ^ Andreoli, V.; Maffei, F.; Montanaro, N.; Morandini, G. (Feb 1977). "Double-blind cross-over clinical comparison of two 2'-chloro benzodiazepines: 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (chlordesmethyldiazepam) versus 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) in neurotic anxiety.". Arzneimittelforschung 27 (2): 436–9. PMID 16622. 
8. ^ Kostowski, W.; Płaźnik, A.; Puciłowski, O.; Trzaskowska, E.; Lipińska, T. (1981). "Some behavioral effects of chlorodesmethyldiazepam and lorazepam.". Pol J Pharmacol Pharm 33 (6): 597–602. PMID 6127668. 
9. ^ Curatolo, P.; Cusmai, R.; Trasatti, G.; Sciarretta, A. (1985). "[Effects of intravenous administration of chlordesmethyldiazepam on paroxysmal intercritical activity in various electroclinical forms of infantile epilepsy]". Riv Neurol 55 (6): 377–86. PMID 3938567. 
10. ^ Bertin, I.; Colombo, G.; Furlanut, M.; Benetello, P. (1989). "Double-blind placebo cross-over study of long-acting (chlordesmethyldiazepam) versus short-acting (lorazepam) benzodiazepines in generalized anxiety disorders.". Int J Clin Pharmacol Res 9 (3): 203–8. PMID 2568350. 
11. ^ Rocca, P.; Fonzo, V.; Scotta, M.; Zanalda, E.; Ravizza, L. (May 1997). "Paroxetine efficacy in the treatment of generalized anxiety disorder.". Acta Psychiatr Scand 95 (5): 444–50. doi:10.1111/j.1600-0447.1997.tb09660.x. PMID 9197912. 
12. ^ Manani, G.; Baldinelli, L.; Cordioli, G.; Consolati, E.; Luisetto, F.; Galzigna, L. (1995). "Premedication with chlordemethyldiazepam and anxiolytic effect of diazepeam in implantology". Anesth Prog 42 (3–4): 107–12. PMC 2148912. PMID 8934975. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2148912. 
13. ^ Cazzato, G.; Gioseffi, M.; Torre, P.; Coppola, N. (Nov-Dec 1982). "[Prevention and therapy of delirium tremens with tiapride and chlordesmethyldiazepam]". Riv Neurol 52 (6): 331–42. PMID 6130594. 
14. ^ ^{a b} Bareggi, SR.; Truci, G.; Leva, S.; Zecca, L.; Pirola, R.; Smirne, S. (1988). "Pharmacokinetics and bioavailability of intravenous and oral chlordesmethyldiazepam in humans". Eur J Clin Pharmacol 34 (1): 109–12. doi:10.1007/BF01061430. PMID 2896126. 
15. ^ Dal Bo, L.; Marcucci, F.; Mussini, E.; Perbellini, D.; Castellani, A.; Fresia, P. (1980). "Plasma levels of chlorodesmethyldiazepam in humans". Biopharm Drug Dispos 1 (3): 123–6. doi:10.1002/bdd.2510010306. PMID 6778522. 
16. ^ Bareggi, SR.; Nielsen, NP.; Leva, S.; Pirola, R.; Zecca, L.; Lorini, M. (1986). "Age-related multiple-dose pharmacokinetics and anxiolytic effects of delorazepam (chlordesmethyldiazepam)". Int J Clin Pharmacol Res 6 (4): 309–14. PMID 2875955. 
17. ^ Bareggi, SR.; Pirola, R.; Leva, S.; Zecca, L. (1986). "Pharmacokinetics of chlordesmethyldiazepam after single-dose oral administration in humans". Eur J Drug Metab Pharmacokinet 11 (3): 171–4. doi:10.1007/BF03189844. PMID 3102240. 
18. ^ Bareggi, SR.; Pirola, R.; Truci, G.; Leva, S.; Smirne, S. (Apr 1988). "Effect of food on absorption of chlordemethyldiazepam". Arzneimittelforschung 38 (4): 561–2. PMID 2900012. 
19. ^ Sennesael, J.; Verbeelen, D.; Vanhaelst, L.; Pirola, R.; Bareggi, SR. (1991). "Pharmacokinetics of intravenous and oral chlordesmethyldiazepam in patients on regular haemodialysis". Eur J Clin Pharmacol 41 (1): 65–8. doi:10.1007/BF00280109. PMID 1782980. 
20. ^ Bareggi, SR.; Pirola, R.; Potvin, P.; Devis, G. (1995). "Effects of liver disease on the pharmacokinetics of intravenous and oral chlordesmethyldiazepam". Eur J Clin Pharmacol 48 (3–4): 265–8. PMID 7589052.