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2018 | 109 | 14-25
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Azapirones for the treatment of anxiety – an overview

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Anxiety disorders belong to the most common psychiatric diagnosis. Over the years, benzodiazepines were considered the gold standard for pharmacological treatment of anxiety. They are effective anxiolytics, but unfortunately the long-term use of benzodiazepines is accompanied by many adverse events. An alternative to classical anxiolytics is a relatively new class of psychotherapeutic drugs – azapirones. They are 5-HT1A partial agonists commonly used in the treatment of generalized anxiety disorder and as augmentation for SSRI in social anxiety disorder and depression. Due to the high ratio of benefits to risk, azapirones are extensively studied for their use in other disease entities. The aim of this article was to overviewed current information on azapirones. Their history of development, mechanism of action, pharmacokinetics, interactions, clinical use and their role in the modern pharmacotherapy of anxiety.
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  • Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4a Chodzki Str., 20-093, Lublin, Poland
  • Faculty of Medicine, Wroclaw Medical University, 5 J. Mikulicza-Radeckiego Str., 50-345 Wroclaw, Poland
  • Faculty of Medicine, Wroclaw Medical University, 5 J. Mikulicza-Radeckiego Str., 50-345 Wroclaw, Poland
  • Department of Clinical Genetics, Medical University of Lublin, 1 Radziwiłłowska Str., 20-080, Lublin, Poland
  • Faculty of Medicine, Wroclaw Medical University, 5 J. Mikulicza-Radeckiego Str., 50-345 Wroclaw, Poland
  • Faculty of Dentistry, Wroclaw Medical University, 26 Krakowska Str., 50-425 Wroclaw, Poland
  • Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4a Chodzki Str., 20-093, Lublin, Poland
  • [1] Artigas F, Developments in the field of antidepressants, where do we go now?, European Neuropsychopharmacology, 25(5) (2015) 657–70.
  • [2] Bandelow B, Zohar J, Hollander E, et al., World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision, The World Journal of Biological Psychiatry, 9(4) (2008) 248–312.
  • [3] Belmer A, Patkar OL, Lanoue V, Bartlett SE, 5-HT1A receptor-dependent modulation of emotional and neurogenic deficits elicited by prolonged consumption of alcohol, Scientific Reports, 8(1) (2018) 2099.
  • [4] Bielski RJ, Cunningham L, Horrigan JP, Londborg PD, Smith WT, Weiss K, Gepirone extended-release in the treatment of adult outpatients with major depressive disorder: a double-blind, randomized, placebo-controlled, parallel-group study, The Journal of clinical psychiatry, 69(4) (2008) 571–7.
  • [5] Blier P, Ward NM, Is there a role for 5-HT1A agonists in the treatment of depression?, Biological Psychiatry, 53(3) (2003) 193–203.
  • [6] Bruno F, Buspirone in the Treatment of Alcoholic Patients, Psychopathology, 22(1) (1989) 49–59.
  • [7] Cadieux RJ, Azapirones: an alternative to benzodiazepines for anxiety, American family physician, 53(7) (1996) 2349–53.
  • [8] Chessick CA, Allen MH, Thase M, et al., Azapirones for generalized anxiety disorder, The Cochrane database of systematic reviews, 3 (2006) CD006115.
  • [9] Chilmonczyk Z, Bojarski A, Pilc A, Sylte I, Functional Selectivity and Antidepressant Activity of Serotonin 1A Receptor Ligands, International Journal of Molecular Sciences, 16(8) (2015) 18474–506.
  • [10] Davari-Ashtiani R, Eslami Shahrbabaki M, Razjouyan K, Amini H, Mazhabdar H, Buspirone Versus Methylphenidate in the Treatment of Attention Deficit Hyperactivity Disorder: A Double-Blind and Randomized Trial, Child Psychiatry & Human Development, 41(6) (2010) 641–8.
  • [11] Davidson JRT, Feltner DE, Dugar A, Management of generalized anxiety disorder in primary care: identifying the challenges and unmet needs, Primary care companion to the Journal of clinical psychiatry, 12(2) (2010).
  • [12] Diaz MR, Chappell AM, Christian DT, Anderson NJ, McCool BA, Dopamine D3-Like Receptors Modulate Anxiety-Like Behavior and Regulate GABAergic Transmission in the Rat Lateral/Basolateral Amygdala, Neuropsychopharmacology, 36(5) (2011) 1090–103.
  • [13] Eison AS, Azapirones: history of development, Journal of clinical psychopharmacology, 10(3 Suppl) (1990) 2S–5S.
  • [14] Fawcett J, Barkin RL, Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression, Journal of Affective Disorders, 51 (1998) 267–85.
  • [15] Feighner JP, Buspirone in the long-term treatment of generalized anxiety disorder, The Journal of clinical psychiatry, 48 Suppl (1987) 3–6.
  • [16] Feighner JP, Boyer WF, Serotonin-1A anxiolytics: an overview, Psychopathology, 22 Suppl 1 (1989) 21–6.
  • [17] Fuhr U, Staib AH, Harder S, et al., Absorption of ipsapirone along the human gastrointestinal tract, British journal of clinical pharmacology, 38(1) (1994) 83–6.
  • [18] Gale CK, Millichamp J, Generalised anxiety disorder, BMJ Clinical Evidence, 2011 (2011).
  • [19] Gammans RE, Stringfellow JC, Hvizdos AJ, et al., Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies, Neuropsychobiology, 25(4) (1992) 193–201.
  • [20] Gobert A, Rivet J-M, Cistarelli L, Melon C, Millan MJ, Buspirone modulates basal and fluoxetine-stimulated dialysate levels of dopamine, noradrenaline and serotonin in the frontal cortex of freely moving rats: activation of serotonin1A receptors and blockade of α2-adrenergic receptors underlie its actions, Neuroscience, 93(4) (1999) 1251–62.
  • [21] Grover M, Camilleri M, Effects on gastrointestinal functions and symptoms of serotonergic psychoactive agents used in functional gastrointestinal diseases, Journal of Gastroenterology, 48(2) (2013) 177–81.
  • [22] Heiser JF, Wilcox CS, Serotonin 5-HT1A Receptor Agonists as Antidepressants, CNS Drugs, 10(5) (1998) 343–53.
  • [23] Hensler JG, Regulation of 5-HT1A receptor function in brain following agonist or antidepressant administration, Life sciences, 72(15) (2003) 1665–82.
  • [24] Holland RL, Wesnes K, Dietrich B, Single dose human pharmacology of umespirone, European Journal of Clinical Pharmacology, 46(5) (1994) 461–68.
  • [25] Hoyer D, Hannon JP, Martin GR, Molecular, pharmacological and functional diversity of 5-HT receptors, Pharmacology Biochemistry and Behavior, 71(4) (2002) 533–54.
  • [26] Imai H, Tajika A, Chen P, et al., Azapirones versus placebo for panic disorder in adults, The Cochrane database of systematic reviews, (9) (2014) CD010828.
  • [27] Keller MB, Hanks DL, Anxiety symptom relief in depression treatment outcomes, The Journal of clinical psychiatry, 56 Suppl 6 (1995) 22–9.
  • [28] Kim SW, Fowler JS, Skolnick P, et al., Therapeutic doses of buspirone block D3 receptors in the living primate brain, The International Journal of Neuropsychopharmacology, 17(8) (2014) 1257–67.
  • [29] Koek W, Patoiseau JF, Assié MB, et al., F 11440, a potent, selective, high efficacy 5-HT1A receptor agonist with marked anxiolytic and antidepressant potential, The Journal of pharmacology and experimental therapeutics, 287(1) (1998) 266–83.
  • [30] Konopka A, Wroński M, Samochowiec J, The medicine’s potentiality in the area of anxiety treatment — history and the present day, Psychiatria, 10(2) (2013) 55–62.
  • [31] Kranzler HR, Buspirone Treatment of Anxious Alcoholics, Archives of General Psychiatry, 51(9) (1994) 720-31.
  • [32] López-Muñoz F, Álamo C, García-García P, The discovery of chlordiazepoxide and the clinical introduction of benzodiazepines: Half a century of anxiolytic drugs, Journal of Anxiety Disorders, 25(4) (2011) 554–62.
  • [33] Mahmood I, Sahajwalla C, Clinical Pharmacokinetics and Pharmacodynamics of Buspirone, an Anxiolytic Drug, Clinical Pharmacokinetics, 36(4) (1999) 277–87.
  • [34] Manahan-Vaughan D, Anwyl R, Rowan MJ, The azapirone metabolite 1-(2-pyrimidinyl)piperazine depresses excitatory synaptic transmission in the hippocampus of the alert rat via 5-HT1A receptors, European journal of pharmacology, 294(2–3) (1995) 617–24.
  • [35] Masdrakis VG, Turic D, Baldwin DS, Pharmacological treatment of social anxiety disorder, Modern trends in pharmacopsychiatry, 29 (2013) 144–53.
  • [36] Mitte K, Noack P, Steil R, Hautzinger M, A Meta-analytic Review of the Efficacy of Drug Treatment in Generalized Anxiety Disorder, Journal of Clinical Psychopharmacology, 25(2) (2005) 141–50.
  • [37] Moraga-Amaro R, Gonzalez H, Pacheco R, Stehberg J, Dopamine receptor D3 deficiency results in chronic depression and anxiety, Behavioural Brain Research, 274 (2014) 186–93.
  • [38] Nash JR, Sargent PA, Rabiner EA, et al., Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study, British Journal of Psychiatry, 193(03) (2008) 229–34.
  • [39] Newton RE, Marunycz JD, Alderdice MT, Napoliello MJ, Review of the side-effect profile of buspirone, The American journal of medicine, 80(3B) (1986) 17–21.
  • [40] Niederhofer H, An open trial of buspirone in the treatment of attention-deficit disorder, Human Psychopharmacology: Clinical and Experimental, 18(6) (2003) 489–92.
  • [41] Ohno Y, Therapeutic Role of 5-HT1A Receptors in The Treatment of Schizophrenia and Parkinson’s Disease, CNS Neuroscience & Therapeutics, 17(1) (2011) 58–65.
  • [42] Parks CL, Robinson PS, Sibille E, Shenk T, Toth M, Increased anxiety of mice lacking the serotonin1A receptor, Proceedings of the National Academy of Sciences of the United States of America, 95(18) (1998) 10734–9.
  • [43] Penington NJ, Fox AP, Effects of LSD on Ca++ currents in central 5-HT-containing neurons: 5-HT1A receptors may play a role in hallucinogenesis, The Journal of pharmacology and experimental therapeutics, 269(3) (1994) 1160–5.
  • [44] Robinson DS, Rickels K, Feighner J, et al., Clinical effects of the 5-HT1A partial agonists in depression: a composite analysis of buspirone in the treatment of depression, Journal of clinical psychopharmacology, 10(3 Suppl) (1990) 67S–76S.
  • [45] Rupprecht R, Eser D, Zwanzger P, Möller H-J, GABA A receptors as targets for novel anxiolytic drugs, The World Journal of Biological Psychiatry, 7(4) (2006) 231–237.
  • [46] Rzewuska M, Leczenie zaburzeń nerwicowych, Farmakoterapia w Psychiatrii i Neurologii, 99(1) (1999) 47–75.
  • [47] Rzewuska M, Pużyński S, Jarema M, et al., Standardy i algorytmy farmakoterapii w zaburzeniach lękowych i obsesyjno-kompulsyjnych, Farmakoterapia w Psychiatrii i Neurologii, 99(1) (1999) 7–18.
  • [48] Sakr A, Andheria M, Pharmacokinetics of buspirone extended-release tablets: a single-dose study, Journal of clinical pharmacology, 41(7) (2001) 783–9.
  • [49] Scheibner J, Trendelenburg A-U, Hein L, Starke K, α 2 -Adrenoceptors modulating neuronal serotonin release: a study in α 2 -adrenoceptor subtype-deficient mice, British Journal of Pharmacology, 132(4) (2001) 925–33.
  • [50] Sramek JJ, Tansman M, Suri A, et al., Efficacy of buspirone in generalized anxiety disorder with coexisting mild depressive symptoms, The Journal of clinical psychiatry, 57(7) (1996) 287–91.
  • [51] Stahl S, 5HT1A receptors and pharmacotherapy. Is serotonin receptor down-regulation linked to the mechanism of action of antidepressant drugs?, Psychopharmacology bulletin, 30(1) (1994) 39–43.
  • [52] Stahl SM, Lee-Zimmerman C, Cartwright S, Morrissette DA, Serotonergic drugs for depression and beyond, Current drug targets, 14(5) (2013) 578–85.
  • [53] Stein MB, Kirk P, Prabhu V, Grott M, Terepa M, Mixed anxiety-depression in a primary-care clinic, Journal of Affective Disorders, 34 (1995) 79–84.
  • [54] Steinberg JR, Anxiety in elderly patients. A comparison of azapirones and benzodiazepines, Drugs & aging, 5(5) (1994) 335–45.
  • [55] Sumiyoshi T, Matsui M, Nohara S, et al., Enhancement of Cognitive Performance in Schizophrenia by Addition of Tandospirone to Neuroleptic Treatment, American Journal of Psychiatry, 158(10) (2001) 1722–5.
  • [56] Sumiyoshi T, Park S, Jayathilake K, Roy A, Ertugrul A, Meltzer HY, Effect of buspirone, a serotonin1A partial agonist, on cognitive function in schizophrenia: A randomized, double-blind, placebo-controlled study, Schizophrenia Research, 95(1–3) (2007) 158–68.
  • [57] Świȩcicki Ł, Praktyczne aspekty farmakoterapii lȩku - Pozycja opipramolu, Psychiatria, 10(2) (2013) 63–6.
  • [58] Taylor DP, Moon SL, Buspirone and related compounds as alternative anxiolytics, Neuropeptides, 19 Suppl (1991) 15–9.
  • [59] Wittchen H-U, Generalized anxiety disorder: prevalence, burden, and cost to society, Depression and Anxiety, 16(4) (2002) 162–171.
  • [60] Azapirones have potential in a wide variety of CNS disorders, Drugs & Therapy Perspectives, 5(1) (1995) 5–7.
  • [61] WHO | The world health report 2001 - Mental Health: New Understanding, New Hope, WHO, (2013).
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