Delorazepam
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|---|---|
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| 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 |
| UNII | O91W32476G |
| KEGG | D07784 |
| ChEMBL | CHEMBL268254 |
| Chemical data | |
| Formula | C15H10Cl2N2O |
| Mol. mass | 304.02 |
| SMILES
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| (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 drugs Diclazepam and 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;[16] 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][17][18] The pharmacokinetics of delorazepam are not altered if it is taken with food, except for some slowing of absorption.[19] 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.[20] Liver disease has a profound effect on the elimination rate of delorazepam, resulting in the half-life almost doubling to 395 hours, whereas healthy patients showed an elimination half-life of 204 hours on average. Caution is recommended when using delorazepam in patients with liver disease.[21]
See also
References
- ↑ 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.
- ↑ "Benzodiazepine Names". non-benzodiazepines.org.uk. Retrieved 2008-12-29.
- ↑ 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.
- ↑ 4.0 4.1 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 14.0 14.1 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.
- ↑ 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.
- ↑ European Journal of Clinical Pharmacology 1988, Volume 34, Issue 1, pp 109-112 'Pharmacokinetics and bioavailability of intravenous and oral chlordesmethyldiazepam in humans' S.R.Bareggi, G.Truci, S.Leva, L.Zecca, R.Pirola, S.Smirne
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.