Brotizolam

Abstract

Brotizolam is a new thienotriazolodiazepine derivative with a pharmacological profile similar to that of benzodiazepines. It is indicated for use as an hypnotic in the management of insomnia, although it also has anticonvulsant, antianxiety and muscle relaxant properties in animals. In clinical trials brotizolam 0.125 to 0.5mg improved sleep in insomniacs similarly to nitrazepam 2.5 and 5mg, flunitrazepam 2mg and triazolam 0.25mg, whilst brotizolam 0.5mg was shown to be superior to flurazepam 30mg in some studies. Brotizolam is an effective hypnotic for hospital patients awaiting surgery, in whom it also reduces anxiety. Brotizolam has an elimination half-life of about 5 hours, which is 'intermediate' compared with the shorter-acting hypnotic, triazolam, and longer-acting benzodiazepines. Consequently, it is able to induce sleep without producing early morning rebound insomnia, and can also maintain sleep throughout the night. Brotizolam at dosages below 0.5mg at night usually produced minimal morning drowsiness; no residual impairment of psychomotor performance occurs following dosages within the recommended range of 0.125 to 0.25 mg/kg. No serious side effects have been reported to date and the most frequently observed adverse experiences are drowsiness, headache and dizziness. Mild rebound insomnia may occur in some patients when treatment is stopped. Thus, brotizolam is a useful hypnotic which can be used in patients who have difficulty in falling asleep and also in patients who are troubled by night-time awakenings. Used in the recommended dosage it may be particularly useful for patients in whom daytime impairment of performance is unacceptable.

2-Amino-4,5-dihydrothiophene-3-carbonitriles: A New Synthesis, Quantum Chemical Studies, and Mannich-Type Reactions Leading to New Hexahydrothieno[2,3-d]pyrimidines

“…Among them, strontium ranelate (Protelos/Osseor, useful for the treatment of osteoporosis, − as a dental pulp-like cell proliferation agent, and as a radiopaque agent for calcium phosphate cement), tinoridine (old but still useful anti-inflammatory drug with a strong antiperoxidative and hepatoprotective activity), − and olanzapine − (Zyprexa, used to treat certain mental disorders such as schizophrenia and bipolar disorder) should be noted (Figure ). In addition, the 2-aminothiophene motif is present in drugs and bioactive molecules such as T-62 (a selective allosteric modulator of the adenosine A receptor), bentazepam (Tiadipona), and brotizolam (Lendormin); − anxiolytic/anticonvulsant agents and skeletal muscle relaxants; and the anticancer drug raltitrexed (Tomudex) − (Figure ). 2-Aminothiophenes are able to act as starting points for the synthesis of a variety of thiophene-containing heterocycles and polycyclic hybrid molecules. − , Moreover, as shown recently, 2-aminothiophenes might find an application in the preparation of functional materials such as electrochemically color switching azomethines, − liquid crystalline materials, oligothiophene-BODIPY hybrids as NIR dyes, organic photovoltaic cells, azodyes, nonlinear optical materials, and azomethine-bridged polythiopheneferrocenes …”

Synthesis, Characterization, Molecular Modeling, and Biological Evaluation of 1,2,4‐Triazole‐pyridine Hybrids as Potential Antimicrobial Agents

“…Among the broad range of heterocyclic that is being explored for expansion of new components in the field of medicinal chemistry, 1,2,4‐triazole‐pyridine hybrids and their fused heterocyclic derivatives have acknowledged significant consideration due to their synthetic and effective biological importance . The triazole is an attractive bridge group, which could connect two pharmacophores to produce novel bifunctional molecules, while it is almost impossible to be hydrolyzed, oxidized, or reduced.…”

Microwave-Assisted Parallel Synthesis of Fused Heterocycles in a Novel Parallel Multimode Reactor

“…To demonstrate the applicability of the new rotors, libraries of thiophenes, oxindoles, and benzimidazoles have been synthesized. Fused thiophenes have gained considerable interest over the decades, being important structural motifs not only in natural compounds but also in dyes, agrochemicals, and pharmaceutically active compounds, such as the analgesic tinoridine or the tranquilizer brotizolam (Lendormin) . The 2-amino derivatives, especially, show a broad scope of applications .…”

“…Fused thiophenes have gained considerable interest over the decades, being important structural motifs not only in natural compounds 12 but also in dyes, 13 agrochemicals, and pharmaceutically active compounds, 14 such as the analgesic tinoridine 15 or the tranquilizer brotizolam (Lendormin). 16 The 2-amino derivatives, especially, show a broad scope of applications. 17 Similarly, oxindoles are part of many natural compounds, such as alkaloids, 18 and as such have attracted the interest of the pharmaceutical industry.…”