Anxiolytics clorazepate

While buspirone does not interact with brain BZD receptors, it has been shown to be superior to placebo and as effective as BZDs for GAD ( 45, 46, 47 and 48) (Table 12-3). In a long-term follow-up study of chronic GAD patients who participated in a 6-month trial comparing clorazepate and buspirone, Rickels and Schweizer ( 33) found a nonsignificant trend for former buspirone-treated patients to report less anxiety than former clorazepate-treated patients. In addition, whereas 65% of the former clorazepate-treated group were still taking anxiolytic medication at 40-month follow-up, no former buspirone patient was taking a psychotropic. 

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,... 

OFFICIAL NAMES Minor tranquilizers (sedative-hyp-notics/anxiolytics)/Benzodiazepines Alprazolam (Xanax) chlordiazepoxide (Librium, Novopoxide) clonazepam (Klonopin) clorazepate (Azene, Tranxene) diazepam (Valium) estazolam (ProSom) flunitrazepam (Rohypnol/illegal in the United States) flurazepam (Dalmane) halazepam (Paxipam) lorazepam (Ativan) midazolam (Versed) oxazepam (Serax) prazepam (Centrax) quazepam (Doral) temazepam (Restoril) triazolam (Halcion)... 

Although the BZs show a robust anxiolytic effect, many of the clinical trials were conducted before the currently used divisions between specific anxiety disorders became available (4). As a result, knowledge of their efficacy in discrete anxiety disorders is incomplete. In clinical practice (48) BZs are widely used for GAD and as prophylactics in situational anxiety, with diazepam (l)historically being the most popular choice. Others in common use are chlordiazepoxide (2), clorazepate (3), lorazepam (4), alprazolam (5), oxazepam (6), bromazepam (7), and clonazepam (8) Response rates are high and the onset of therapeutic effect is immediate. This is an important contrast to the MAOIs, TCAs, and SSRIs, where an anxiolytic effect is not seen for several weeks. Although not specifically approved for this disorder. BZs are also effective in social phobia, with clonazepam (49) showing a superior response rate to that of alprazolam (50). Alprazolam and clonazepam are the only BZs approved for the treatment of panic disor-... 

Clorazepate is a prodrug and possesses no anxiolytic effects until metabolism to DMDZ. Before absorption, clorazepate is metabolized rapidly in the stomach through a pH-dependent process under acidic conditions. 

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. 

An interesting situation arises when the two long-acting anxiolytics, prazepam (No. 16) and clorazepate (No. 4), are considered. Neither drug reaches the systemic circulation in meaningful quantities they are essentially pro-drugs that are converted to DMD with great facility. 

Anxiolytics and hypnotics Benzodiazepines Alprazolam, Bromazepam, Brotizolam, Chlordiazepoxide, Clobazam, Clonazepam, Clorazepate, Clotiazepam, Diazepam, Flunitrazepam, Flurazepam, Ketazolam, Loprazolam, Lorazepam, Lormetazepam, Medazepam, Midazolam, Nitrazepam, Oxazepam, Oxazolam, Quazepam, Temazepam, Triazolam... 

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