Benzodiazepine agonist drugs

A pharmacodynamic interaction involves either inhibition or enhancement of the clinical effects of the victim drug as a consequence of similar or identical end-organ actions. Examples are the increase or decrease of the sedative-hypnotic actions of benzodiazepine agonist drugs due to coadministration of ethanol or... 

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

Figure 19.8 A schematic representation of the GABAa receptor shift hypothesis. This proposes that patients with panic disorder have dysfunctional GABAa receptors such that the actions of drugs that behave as antagonists in normal subjects are expressed as inverse agonism in panic patients. It is unlikely that this theory extends to generalised anxiety disorder (GAD), for which benzodiazepine agonists are highly effective treatments, but it could explain why these drugs are relatively ineffective at treating panic disorder. (Based on Nutt et al. 1990)...

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. 

Buspirone has selective anxiolytic effects, and its pharmacologic characteristics are different from those of other drugs described in this chapter. Buspirone relieves anxiety without causing marked sedative, hypnotic, or euphoric effects. Unlike benzodiazepines, the drug has no anticonvulsant or muscle relaxant properties. Buspirone does not interact directly with GABAergic systems. It may exert its anxiolytic effects by acting as a partial agonist at brain 5-HTia receptors, but it also has affinity for brain dopamine D2 receptors. Buspirone-treated patients show no... 

Lesopitron is a non-benzodiazepine anxiolytic drug. Its structure is similar to that of buspirone, and it is an agonist at central serotonin (5-HT1A) receptors. 

Anxiolytics are drugs used for the treatment of anxiety disorders. Apart from benzodiazpines, a frequently used anxiolytic is the 5HT1A (serotonin) receptor agonist buspiron, which has no sedative, amnestic or muscle-relaxant side effects, but whose action takes about a week to develop. Furthermore, it is less efficaceous than the benzodiazepines. Buspiron s mechanism of action is not fully understood. 

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. 

Benzodiazepines have a low risk for abuse in anxiety disorder patients without a history of alcohol or other substance abuse. Among the benzodiazepines there may be a spectrum of abuse liability, with drugs that serve as prodrugs for desmethyldiazepam (e.g., clorazepate), slow-onset agents (e.g., oxazepam), and partial agonists (e.g., abecarnil) having the least potential for abuse. However, there is no currently marketed benzodiazepine or related drug that is free of potential for abuse. 

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