Is Chlordiazepoxide the Rational Choice Among Benzodiazepines?

Abstract

Diazepam is frequently the subject of review by various agencies and institutions charged with determining whether or not to substitute another, more economical drug--in most instances, chlordiazepoxide. A review of the comparative literature has shown that, on clinical and pharmacokinetic grounds, chlordiazepoxide is not the drug of choice for all clinical indications recommended for the benzodiazepines as a class, particularly for use as an antianxiety agent. There is evidence that the antianxiety effect of chlordiazepoxide is related to the appearance of its two active metabolites, which may explain the observed delay in its onset of action. When chlordiazepoxide's reduced clearance in the elderly and in patients with liver disease is considered along with its limited range of indications, substitution of diazepam with chlordiazepoxide is clearly not reasonable. Diazepam and lorazepam are preferred choices in acute anxiety because they are themselves active anxiolytics. Oxazepam is recommended in alcoholic cirrhotics because its plasma clearance does not seem to be significantly affected by liver disease. Diazepam is recommended for chronic anxiety because of the rapid onset of action of diazepam itself and the smooth transition to the nondrug state via its longer-acting active metabolite.

Syntheses of 1,5-Benzothiazepines: Part-50: 8-Substituted 2,3/2,5-dihydro-2,4-diaryl-1,5-benzothiazepines as Potential Antimicrobial Agents

“…The chemotherapeutic utilization of halogenated 1,4-and 1,5-benzodiazepines, e.g. chlordiazepoxide [1], clobazam [2], triflubazam [3] as CNS drugs prompted the study of analogous benzothiazepine compounds. Interestingly, these compounds have been found to show pronounced cardiovascular activities, the most prominent emergent drug being diltiazem [4], which has been found to be useful in the treatment of angina pectoris and is useful in coronary vasodilation and regulation of Ca 2+ concentration.…”

Initial study of methylclonazepam in generalized anxiety disorder

“…Following the introduction of chlordiazepoxide in 1960, numerous compounds have been marketed, differing in their potency and pharmacokinetic properties (Greenblatt et al 1983 a). Controversy still exists, however, with respect to the more subtle clinical differences which seem to exist among compounds (Baskin and Esdale 1982;Greenblatt et al 1983 b;Lapierre 1983;Chouinard et al 1983;Straw 1983). As a group, the benzodiazepines are clearly superior in anxiolytic activity to the other classes of antianxiety agents and are much less toxic at clinically useful doses (Rickels 1983).…”