Agonists benzodiazepine receptor interactions with

This section describes the partial agonists and the nonbenzodiazepine drugs that act at the benzodiazepine receptor. What these drugs have in common is that their development has been driven by the search for effective anxiolytics that do not have the adverse effects of sedation, amnesia, ataxia, interaction with alcohol, or the problems of tolerance, dependency, and withdrawal seen with classic benzodiazepines. These problems have been addressed by the development of partial agonists, subtype-selective ligands, and other drugs, the cyclopyrrolones, which do not seem to cause these problems. 

Buspirone is a partial agonist at serotonin type 1A (5-HTj ) receptors. Unlike benzodiazepines, barbiturates, and alcohol, buspirone does not interact with the GABA receptor or chloride ion channels. Thus, it does not produce sedation, interact with alcohol, impair psychomotor performance, or pose a risk of abuse. There is no cross-tolerance between benzodiazepines and buspirone, so benzodiazepines cannot be abruptly replaced with buspirone. Likewise, buspirone cannot be used to treat alcohol or barbiturate withdrawal and detoxification. Like the antidepressants, buspirone has a relatively slow onset of action. 

It belongs to azapirones which is chemically and pharmacologically distinct class. It acts as a partial agonist at serotonin and dopamine receptors and having no hypnotic and sedative action. It does not interact with benzodiazepine receptor or modify GABA-ergic transmission. 

Other drugs The anxiolytic ding buspirone interacts with the S-HT, subclass of brain serotonin receptors as a partial agonist, but the precise mechanism of its anxiolytic effect is unknown. The hypnotics zolpidem and zaleplon are not benzodiazepines but appear to exert their CNS effects via interaction with certain benzodiazepine receptors, classified as BZ, or omega, subtypes their CNS depressant effects are antagonized by flumazenil. 

Using molecular biological techniques, point mutations of the a subunits have revealed that the sedative effects of the benzodiazepines likely result from an Interaction with the ai subunit, whereas the anxiolytic effects result from an interaction at the 02 subunit (27,28), as shown in Figure 15.10 and Table 15.3. Nonbenzodiazepine receptor agonists, such as the sedative-hypnotics indiplon, zaleplon, zolpicone, and zolpidem (see Chapter 19), are ai subunit-preferring ligands, as shown in Table 15.3 (29). 

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