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Anxiolytics pp 13–25Cite as

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Buspirone

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Part of the Milestones in Drug Therapy book series (MDT)

Abstract

Originally envisioned as a novel antipsychotic agent [1], buspirone {8-[4-[4- (2-pyrimidinyl)-1-pipirazinyl] butyl] -8-azapiro[4, 5]decane-7,9-dione} failed to show antipsychotic efficacy in ten hospitalized schizophrenic inpatients receiving a mean dose of 1,470 mg [2]. On the contrary, a growing appreciation for buspirone’s unexpected anxiolytic, but not antipsychotic properties [3, 4] ultimately influenced the nature of its prospective development. The clinical observations of buspirone’s anxiolytic and subsequently discovered antidepressant effects have been correlated with the compound’s acute agonist properties at serotonin (5HT, or 5-hydroxytryptamine) lA receptors at serotonergic synapses in the dorsal raphe nucleus and hippocampus [5-7]. Thus, the potent 5-HT1A agonist buspirone (Buspar) made its U.S. debut in 1986 as a non-benzodiazepine anxiolytic of the azapirone class. Buspirone is the first, and as yet only member of the azapirone family to achieve an approved indication for the treatment of generalized anxiety disorder (GAD). Several other azapirones have been tested, and some continue in clinical development (e.g. gepirone and tandospirone), while others have been dropped from further development (e.g. transdermal buspirone and ipsapirone). The following is primarily a discussion of the neuropharmacologic mechanisms and relevant clinical implications of buspirone’s theorized attenuation of central serotonergic neurotransmission in regard to defining therapeutic efficacy for generalized anxiety disorder (GAD), for disorders encompassing states of mixed anxiety/depression (MAD) including those with subsyndromal features and for major depressive disorder (MDD). The validity and clinical advantage of the widespread use of buspirone augmentation of antidepressants will also be reviewed.

Keywords

  • Generalize Anxiety Disorder
  • Major Depressive Disorder
  • Dorsal Raphe Nucleus
  • Generalize Anxiety Disorder Patient
  • Serotonergic Antidepressant

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Author information

Authors and Affiliations

  1. Clinical Neuroscience Research Center, 8899, University Center Lane, Suite 130, San Diego, California, 92122, USA

    Darius K. Shayegan

  2. Department of Psychiatry, University of California San Diego, USA

    Stephen M. Stahl

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  1. Darius K. Shayegan
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  2. Stephen M. Stahl
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Editors and Affiliations

  1. Institut de Recherche Pierre Fabre, Parc Industriel de la Chartreuse, Castres, 81100, France

    Dr. Mike Briley

  2. Psychopharmacology Unit School of Medical Science, University of Bristol, University Walk, Bristol, BS8 1TD, UK

    Professor David Nutt

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Shayegan, D.K., Stahl, S.M. (2000). Buspirone. In: Briley, M., Nutt, D. (eds) Anxiolytics. Milestones in Drug Therapy. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8470-9_2

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  • DOI: https://doi.org/10.1007/978-3-0348-8470-9_2

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