GABA-benzodiazepine agonist drugs

Table 3 Options for Pharmacodynamic Endpoints in Kinetic-Dynamic Studies of GABA-Benzodiazepine Agonist Drugs...

Changes have also been reported to occur in the sub-unit composition of the GABA-A receptor following chronic exposure to barbiturates, neurosteroids, ethanol and benzodiazepine agonists. These changes may underlie the development of tolerance, physical dependence and the problems which are associated with the abrupt withdrawal of such drugs. 

Although benzopiperazinones (l,2,3,4-tetrahydroquinoxalin-2-ones) are structurally related to benzodiazepines, their use in drug discovery is less well established. Examples of biological activity of benzopiperazinones include their action as inhibitors of aldose reductase [208], as partial agonists of the y-aminobutyric acid (GABA)/benzodiazepine receptor complex [209, 210], and as angiotensin II receptor antagonists [211]. In addition, derivatives with antiviral acti vity associated vfith HIV have been reported [212, 213]. 

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

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