Anxiolytic Actions Of Benzodiazepines

Benzodiazepines and their Mechanisms of Action

Benzodiazepines are among the most common medications prescribed for treating various conditions, including anxiety, insomnia, alcohol withdrawal, and seizures. In this sense, they are a group of Central Nervous System (CNS) depressants that induce the feeling of calm, sleep, and drowsiness. According to Guina & Merrill (2018), Benzodiapines’ mechanism of action entails interacting with gamma-aminobutyric (GABA) receptors, the primary inhibitory neurotransmitters in the central nervous system. In this sense, they create an impact by facilitating the binding of inhibitory neurotransmitter GABA at various GABA receptors throughout the central Nervous System. The process of binding GABA neurotransmitters in different receptors in the CNS results in anxiolytic (anxiety-reducing) and hypnotic/soporific (sleep-inducing) effects. However, physicians prescribe benzodiazepines (BZDs) for short-term treatment of anxiety and insomnia due to their potential adverse effects, including recklessness, dependency, irritability, and amnesia.

Buspirone

What is buspirone’s mechanism of action?

Buspirone is a commonly prescribed medication for treating anxiety and augmenting persistent depression. According to Wilson & Tripp (2021), the original purpose of buspirone was to treat psychosis. However, it emerged ineffective for psychosis but possessed useful anxiolytic features that rendered it ideal for treating anxiety. Further, buspirone is a promising anxiolytic drug because of its minimal single-effect profile compared to other anxiolytic regimens such as Benzodiazepines.

Buspirone is in the class of azapirones because it has a strong affinity for serotonin 5HT1a receptors and acts as a partial agonist on these receptors. Wilson & Tripp (2021) contend that the drug has a weak affinity for serotonin 5HT2 receptors and is a partial antagonist of D2 dopamine autoreceptors. Further, buspirone does not influence benzodiazepine GAMA receptors. In this sense, it has no hypnotic, anticonvulsant, or muscle relaxant effects like benzodiazepines. Therefore, it is effective for treating generalized anxiety.

Why might it be used to augment vs. as the primary treatment?

As stated earlier, buspirone acts as a partial agonist on serotonin 5HT1a receptors. Also, it antagonizes dopamine to a lesser extent (Walls et al., 2018). Unlike benzodiazepines, buspirone does not affect GABA receptors, meaning they have no hypnotic, anticonvulsant, or muscle relaxant effects. Therefore, it can only treat generalized anxieties. However, buspirone is a popular augmentative antidepressant because it has a different mechanism of action compared to other anxiolytic regimens. In this sense, it activates serotonin, leading to mood improvement and sleep management.

What is a serotogenic hypnotic?

A serotogenic hypnotic is a class of drugs that inhibit serotonin reuptake, increasing serotonin levels in the brain. According to Mayo Clinic (2019), serotonin is a chemical messenger in the brain which carries signals between the brain nerve cells (neurons). As a result, inhabiting the chemical’s reuptake into neurons makes it more available to improve message transmission between neurons. An example of serotogenic hypnotic drugs is the selective serotonin reuptake inhibitors (SSRIs), a class of drugs that contains different medications, including citalopram, fluoxetine, sertraline, and paroxetine.

How a serotogenic hypnotic works in insomnia

Some antidepressants, including selective serotonin reuptake inhibitors (SSRI), can play a significant role in treating insomnia and improving sleep. DerSarkissian (2022) argues that SSRIs play a double role in improving sleep and mood by inhibiting serotonin reuptake into neurons. In this sense, SSRIs provide the first-line treatment options for depressive disorders. Therefore, they are effective for treating anxiety and depression-related insomnia. However, patients must adhere to precautions because some stimulating SSRIs, such as Fluoxetine, can increase awakening and impair sleep continuity.

References

DerSarkissian, C. (2022, March 27). Sleep disorders: Sleep disorders linked to depression. WebMD. https://www.webmd.com/depression/sleep-problems-and-depression

Guina, J., & Merrill, B. (2018). Benzodiazepines I: Upping the care on downers: The evidence of risks, benefits, and alternatives. Journal of Clinical Medicine, 7(2), 17. https://doi.org/10.3390/jcm7020017

Mayo Clinic. (2019, September 17). Selective Serotonin Reuptake Inhibitors (SSRIs). Mayo Clinic; Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/depression/in-depth/ssris/art-20044825

Walls, R. M., Hockberger, R. S., Gausche-Hill, M., & Bakes, K. M. (2018). Rosen’s emergency medicine: concepts and clinical practice (9th ed.). Elsevier.

Wilson, T. K., & Tripp, J. (2021, August 12). Buspirone. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK531477/

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