Cinazepam (BD-798, sold under brand name Levana) is an atypical

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

derivative. It produces pronounced

hypnotic A hypnotic (from Ancient Greek, Greek ''Hypnos'', sleep), also known as a somnifacient or soporific, and commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to sleep induction, induce sleep and to trea ...

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

, and

anxiolytic An anxiolytic (; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

effects with minimal

myorelaxant A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therap ...

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s. In addition, unlike many other benzodiazepine and

nonbenzodiazepine Nonbenzodiazepines (), sometimes referred to colloquially as Z-drugs (as many of their names begin with the letter "z"), are a class of psychoactive, depressant, sedative, hypnotic, anxiolytic drugs that are benzodiazepine-like in uses, such as f ...

hypnotics such as

diazepam Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety disorder, anxiety, seizures, alcohol withdrawal syndr ...

flunitrazepam Flunitrazepam, sold under the brand name Rohypnol among others, is a benzodiazepine used to treat severe insomnia and assist with anesthesia. As with other hypnotics, flunitrazepam has been advised to be prescribed only for short-term use or by ...

, and

zopiclone Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine, specifically a cyclopyrrolone, used to treat difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone ...

, cinazepam does not violate sleep architecture, and the continuity of

slow-wave sleep Slow-wave sleep (SWS), often referred to as deep sleep, is the third stage of non-rapid eye movement sleep (NREM), where electroencephalography activity is characterised by slow delta waves. Slow-wave sleep usually lasts between 70 and 90 mi ...

and

REM sleep Rapid eye movement sleep (REM sleep or REMS) is a unique phase of sleep in mammals (including humans) and birds, characterized by random rapid movement of the eyes, accompanied by low muscle tone throughout the body, and the propensity of the s ...

are proportionally increased. As such, cinazepam produces a sleep state close to physiological, and for that reason, may be advantageous compared to other, related drugs in the treatment of

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

and other

sleep disorder A sleep disorder, or somnipathy, is a medical disorder affecting an individual's sleep patterns, sometimes impacting physical, mental, social, and emotional functioning. Polysomnography and actigraphy are tests commonly ordered for diagnosing sle ...

s. Cinazepam has an order of magnitude lower

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for the

benzodiazepine receptor The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous Ligand (biochemistry), ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Accurate regul ...

of the GABA_A complex relative to other well-known hypnotic benzodiazepines such as

nitrazepam Nitrazepam, sold under the brand name Mogadon among others, is a Hypnotic, hypnotic drug of the benzodiazepine class used for short-term relief from severe, disabling anxiety and insomnia. It also has sedative (calming) properties, as well as am ...

and

phenazepam Phenazepam (also known in Russia as bromdihydrochlorphenylbenzodiazepine) is a benzodiazepine drug, first developed in the Soviet Union in 1975, and now produced in Russia and several other countries. Phenazepam is used in the treatment of vario ...

. Moreover, in mice, it is rapidly

metabolized Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

, with only 5% of the base compound remaining within 30 minutes of administration. As such, cinazepam is considered to be a benzodiazepine

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

; specifically, to 3-hydroxyphenazepam, as the main

active metabolite An active metabolite, or pharmacologically active metabolite is a biologically active metabolite of a xenobiotic substance, such as a drug or environmental chemical. Active metabolites may produce therapeutic effects, as well as harmful effects. ...

Synthesis

The reaction between 2-amino-5-bromo-2'-chlorobenzophenone 0773-49-1(1) and bromoacetyl bromide 98-21-0gives 5-bromo-2'-chloro-2-bromoacetamido-benzophenone, PC33695403 (2). Finkelstein reaction with sodium iodide gives PC11375008 (3). Reaction with hydroxylamine preferentially causes alkylation by displacement of the leaving group than oxime formation. Hence, the product of this step is PC129780422 (4). Ring closure in acid led to Phenazepam 4-Oxide 177751-52-8(5). Treatment with acetic anhydride and Polonovski rearrangement gave PC630731 (6). Saponification of the ester yielded 3-Hydroxyphenazepam 0030-11-4(7). Treatment with succinic anhydride completed the synthesis of Cinazepam (8).

References

Abandoned drugs Anxiolytics Benzodiazepines 2-Chlorophenyl compounds Hypnotics Bromobenzene derivatives Carboxylic acids Prodrugs {{sedative-stub

Synthesis

See also

References