Anxiolytic; muscle relaxant (skeletal); anticonvulsant; ligand for the GABAA receptor benzodiazepine modulatory site. Controlled substance (depressant).
ChEBI: A 1,4-benzodiazepinone that is 1,3-dihydro-2H-1,4-benzodiazepin-2-one substituted by a chloro group at position 7, a hydroxy group at position 3 and phenyl group at position 5.
(A) Suspend 10 g of 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2one 4-oxide in 150 ml of acetic anhydride and warm on a steam bath with stirring until all the solid has dissolved. Cool and filter off crystalline, analytically pure 3-acetoxy-7-chloro-1,3-dihydro-5-phenyl-2H-1,4benzodiazepin-2-one, melting point 242°C to 243°C.
(B) Add to a suspension of 3.4 g of 3-acetoxy-7-chloro-1,3-dihydro-5-phenyl2H-1,4-benzodiazepin-2-one in 80 ml of alcohol.6 ml of 4 N sodium hydroxide. Allow to stand after complete solution takes place to precipitate a solid. Redissolve the solid by the addition of 80 ml of water. Acidify the solution with acetic acid to give white crystals. Recrystallize from ethanol to obtain 7chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one, melting point 203°C to 204°C.
Serax (Alpharma); Zaxopam (Quantum Pharmics).
Odorless creamy-white to pale-yellow powder or white crystalline solid. Bitter taste. pH (2% aqueous suspension) 4.8-7.
Oxazepam, 7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazpin-2-one (Serax), isan active metabolite of both chlordiazepoxide and diazepamand can be considered a prototype for the 3-hydroxy benzo-diazepines. It is much more polar than diazepam. Oxazepam is rapidlyinactivated to glucuronidated metabolites that are excretedin the urine. Thus, the half-life of oxazepam is about 4 to 8hours, and it is marketed as a short-acting anxiolytic. As aresult, its cumulative effects with chronic therapy are muchless than with long-acting benzodiazepine such as chlordiazepoxideand diazepam.
OXAZEPAM is stable in light and is non hygroscopic. OXAZEPAM is stable in neutral solution. OXAZEPAM is hydrolyzed by acids and bases.
Flash point data for OXAZEPAM are not available; however, OXAZEPAM is probably combustible.
The half-life of oxazepam is approximately 4 to 8 hours, and cumulative effects with chronic therapy
are much less than with long-acting benzodiazepines, such as chlordiazepoxide and diazepam. Lorazepam is the
2′-chloro derivative of oxazepam and has a similarly short half-life (2–6 hours) and pharmacological activity.
Potentially hazardous interactions with other drugs
Antibacterials: metabolism possibly increased by
rifampicin.
Antipsychotics: enhanced sedative effects; risk of
serious adverse effects in combination with clozapine.
Antivirals: possibly increased concentration with
ritonavir.
Sodium oxybate: enhanced effects of sodium oxybate
- avoid.
Ulcer-healing drugs: metabolism inhibited by
cimetidine.
Oxazepam is an active metabolite of both chlordiazepoxide and diazepam and is marketed separately, as a shortacting anxiolytic agent. Oxazepam is rapidly inactivated to glucuronidated metabolites that are excreted in the urine.
