Clorazepate anticonvulsant

Anticonvulsant As adjunctive therapy in the management of partial seizures (clorazepate) adjunctively in status epilepticus and severe recurrent convulsive seizures (diazepam IV) adjunctively in convulsive disorders (diazepam oral). Preoperative For preoperative apprehension and anxiety (chlordiazepoxide, diazepam IV) prior to cardioversion for the relief of anxiety and tension and to diminish patient s recall (diazepam IV) adjunctively prior to endoscopic procedures for apprehension, anxiety, or acute stress reactions and to diminish patient s recall (diazepam) ... 

BZDs differ considerably in potency, which refers to the milligram dose needed to produce a given clinical effect. These differences are in part due to differences in receptor site affinity. If given in the appropriate dose, any BZD may exert anxiolytic, hypnotic, or anticonvulsant effects. For example, anxiolytic BZDs, such as clorazepate and diazepam, are often used as hypnotics when anxiety is a prominent symptom associated with insomnia. 

Clorazepate (Tranxene) [C-IV] [Anxiolytic, Anticonvulsant, Sedarive/Hypnoric/Benzoaiazepine] Uses Acute anxiety disorders,... 

Benzodiazepines exert central depressant effects on spinal reflexes, in part mediated by the brainstem reticular system.3 For example, chlordiazepoxide depresses the duration of electrical after-discharge in the limbic system. Most benzodiazepines elevate the seizure threshold and therefore may be used as anticonvulsant medications. Diazepam, clonazepam, and clorazepate may be prescribed for this therapeutic purpose. 

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). 

Diazepam. Like clorazepate, diazepam is converted into nordazepam (4f) by AT-demeth-ylation (Fig. 6.3) and to oxazepam (4g). Direct hydroxylation produces N-methyl-oxazepam (4h). The low concentrations of (4g) and (4h) preclude their role as active anticonvulsants (41). Unlike clorazepate, diazepam is bioactive. The transformation of diazepam to nordazepam is less complete, in that 62-73% of diazepam is excreted in the urine and about 10% is found in the feces (41). Diazepam is rapidly absorbed when taken orally (30-90 min) or rectally (10-60 min). 

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. 

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