Nitrazepam anticonvulsant

A long half-life is needed for a BZ to be effective as an anticonvulsant to avoid a withdrawal effect. Clonazepam, nitrazepam, and nordazepam are the BZs most often used for their anticonvulsant effects, al-... 

The quinazolones methaqualone (129 R = Me) and mecloqualone (129 R = Cl) are anticonvulsants, but little structural variation can be made without loss of activity. The benzodiazepines which were first introduced as antianxiety drugs have proved useful as anticonvulsants, particularly diazepam (135) and nitrazepam (136). 

Most of the sedative-hypnotics are capable of inhibiting the development and spread of epileptiform activity in the central nervous system. Some selectivity exists in that some members of the group can exert anticonvulsant effects without marked central nervous system depression (although psychomotor function may be impaired). Several benzodiazepines—including clonazepam, nitrazepam, lorazepam, and diazepam—are sufficiently selective to be clinically useful in the management of seizure states (see Chapter 24 Antiseizure Drugs). Of the barbiturates, phenobarbital and metharbital (converted to phenobarbital in the body) are effective in the treatment of generalized tonic-clonic seizures. 

The antianxiety effects of chlordiazepoxide (165) were described in 1960 and this compound was followed by diazepam (135). These two drugs have captured 75% of the market for sedatives in the USA. Other benzodiazepines used as antianxiety agents include oxazepam (166 R = H), a metabolite of diazepam that is better tolerated, lorazepam (166 R = Cl) and potassium clorazepate (167). Prazepam is the iV-cyclopropylmethyl analogue of diazepam. The benzodiazepines have other therapeutic applications, many being used for inducing sleep, diazepam and nitrazepam are anticonvulsants and flurazepam (168) is both an antianxiety agent and a potent hypnotic. Thieno- and pyrazolo-1,4-diazepinones isosteric with diazepam have similar pharmacological properties (B-81 Ml 10604). 

Clinically important, potentially hazardous interactions with alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

Clobazam and Nitrazepam. Two new investigational benzodiazepines appear to be safe and effective as anticonvulsants. However, these agents have long elimination half-lives that increase the potential not only for drug accumulation but also for residual side effects. 

Reduction of the nitro group via hydrogen abstraction from the medium occurs, for example, with nitrated benzodiazepines such as the anticonvulsant nitrazepam and the hypnotic flunitrazepan. Stepwise reduction down to the amino level takes place under anaerobic conditions different processes occur in the presence of oxygen (Busker et al., 1987 Givens et al., 1986). The more common case, however, involves... 

Benzodiazepines (Bzs) are an important class of pharmaceutical product used for their anticonvulsant, hypnotic, tranquilizing, and muscle relaxant properties. The most frequently used are diazepam, nitrazepam, and chlor-diazepoxide. It is necessary to determine their quantity in urine, the metabolites as well as the quantities and nature of these drugs. Because the concentration of these drugs and metabolites in urine is low, the ELISA technique140 is recommended for their assay. The technique assures good selectivity, sensitivity, and a low detection limit (0.3 pg/ml). The reliability of the analytical information as well as the rapidity of the analysis make the ELISA technique suitable for automation. It is simple and quick to use in the laboratory as a routine analytical technique. 

With an understanding of the mechanisms and metabolic reactions of these drugs, newer drug design concepts were applied in later synthetic phases. It is not surprising that compounds were developed in which certain pharmacologic properties became elevated or subdued (but never eliminated). Flurazepam (No. 7, Table 12-8), nitrazepam (No. 13), and triazolam (No. 22) became widely used as hypnotics clonazepam (No. 3) is used almost exclusively as an anticonvulsant, while diazepam (No. 6), clorazepate (No. 4), lorazepate (No. 19), prazepam (No. 16), and aprazolam (No. 19) are marketed primarily as anxiolytics. 

Experimentally, benzodiazepines inhibit some types of seizure activity. Clonazepam, nitrazepam, and nordazepam have more selective anticonvulsant activity than most other benzodiazepines. Benzodiazepines also suppress ethanol-withdrawal seizures in human beings. However, the development of tolerance to the anticonvulsant effects has limited the usefulness of benzodiazepines in the treatment of recurrent seizure disorders (see Chapter 19). 

Windorfer A, Sauer W. Drug interactions during anticonvulsant Iher y in childhood diphe-nylhydantoin, primidone, phenobarbitone, clonazepam, nitrazepam, carbamazepin and dipro-pylacetate. Neuropadiatrie (1977) 8, 29-41. 

Temazepam (XIV) was reported to have marked and prolonged anticonvulsant effects in rabbits and also to be of value in the treatment of insomniac patients with neurosis or endogenous depression. Nitrazepam (XVa) was reported as a useful agent in the treatment of children with resistant myclonic seizures, The utility of clonazepam (XVb) as an anticonvulsant agent was the subject of a symposium. 

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