Benzodiazepine derivatives anticonvulsant activity

Further new competitive AMPA antagonists include the imidazo-fused 23-benzodiazepine derivative 103. This compound showed excellent anticonvulsant activity and other activities indicative of possible therapeutic significance in human stroke and Parkinson k disease <00BMC2127>. An efficient synthesis of fluorine-containing H-1,4-diazepino[6,5-/t]quinolines has been described based on iV,/V-dimethyl-5,7-bis(trifluoroacetyl)-8-quinolylamine and an aromatic nucleophilic displacement with 1,2-ethylenediamine, followed by cyclocondensation <00S1822>. 

Benzodiazepine derivatives are thought to exert their anticonvulsant activity by facilitating GABAer-gic transmission. Substances that inhibit the synthesis of GABA (e.g., isoniazid) or block the GABA recognition site (e.g., bicuculline) cause convulsions (Figure 65.6). 

Clobazam. Clobazam (4d) differs from the previous benzodiazepines, given that it is a 1,5-benzodiazepine rather than a 1,4-derivative. It was demonstrated that N-desmethyl-clobazam (4k) possessed anticonvulsant activity (50,51). 

Benzodiazepines are an important class of pharmacologically active compounds finding application as anticonvulsant, antianxiety, and hypnotic agents. Benzodiazepine derivatives also find commercial use as dyes for acrylic fibers and as anti-inflammatory agents. Jarikote and coworkers have developed a new and efficient method for the regioselective synthesis of 1,5-benzodiazepines in excellent isolated yields in short reaction times nsing a room-temperature ionic liquid, namely,... 

The pharmacology of benzodiazepine derivatives differs significantly from that of the neuroleptics, in that the benzodiazepines have no psychoplegic (antipsychotic) activity and cause no extrapyramidal, autonomic, or endocrine side effects. In addition, unlike the neuroleptics, which lower the seizure threshold, these substances are anticonvulsants. In addition, they are anxiolytics, muscle relaxants, and mild sedatives. Although the benzodiazepine derivatives do not produce pronounced autonomic or CV side effects, they can reduce or block the emotionally induced changes in cardiovascular functions, probably through actions on the limbic system. 

Another benzodiazepine derivative possessing anticonvulsant activity is ORE-8063 (XXIl). The compound inhibits maximal electroshock, pentylenetetrazol and thlosemicarbazide convulsions in laboratory animals . ... 

There has been interest in 2(4)-amino- and 2(4)-thio-benzodiazepines because a number of them show physiological and pharmacological activity (see also Section I). Thus, some 2-amino derivatives can behave as tranquilizers, 2-amino-4-thio derivatives show a variety of activity, some as anticonvulsants, others as stimulants, and certain 2-thio derivatives have antibacterial properties. 

Benzodiazepines and their dihydro derivatives constitute an important class of psychopharmaca [156-161]. In particular, derivatives of benzo[Z>][l,4]diazepines have aroused considerable interest as CNS active anticonvulsant drugs [162-164],... 

Cinoiazepam [inn] is one of the [1,41 benzodiazepines, a BENZODIAZEPINE BINDING-SITE AGONIST, with most of its properties similar to diazepam. It has HYPNOTIC, ANTICONVULSANT and ANXIOLYTIC activity. It has been used orally to treat insomnia and anxiety, cinoxacin [ban, inn, jan, usan] (Clnobac ) is an ANTIMICROBIAL, One of a 4-quinolone family related to nalidixic acid, which, though symthetic, are sometimes described as ANTIBIOTICS. It can be used clinically as an ANTIBACTERIAL, mainly used orally for gut infections. Cinoxate [inn, usan] is a cinnamic acid derivative and can be used in topical sunscreen preparations. 

Compound (XXII) resulted from a study of several 7-trifluoromethoxy and 7-trifluoro methylthio derivatives of 1,4-benzodiazepines When tested for its ability to induce ataxia, to decrease locomotor activity and to afford protection against electroshock and strychnine-induced convulsions in mice, it had activity, potency and acute toxicity similar to those of chlordiazepoxide (XXIII). The utility of XXIII and diazepam (XXIV) as useful anticonvulsants has been demonstrated ... 

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