Gepirone and the Treatment of Panic Disorder

Griebel

European Journal of Pharmacology

2003

258

159

The Mouse Defense Test Battery was developed from tests of defensive behaviors in rats, reflecting earlier studies of both acute and chronic responses of laboratory and wild rodents to threatening stimuli and situations. It measures flight, freezing, defensive threat and attack, and risk assessment in response to an unconditioned predator stimulus, as well as pretest activity and postthreat (conditioned) defensiveness to the test context. Factor analyses of these indicate four factors relating to cognitive and emotional aspects of defense, flight, and defensiveness to the test context. In the Mouse Defense Test Battery, GABA A -benzodiazepine anxiolytics produce consistent reductions in defensive threat/attack and risk assessment, while panicolytic and panicogenic drugs selectively reduce and enhance, respectively, flight. Effects of GABA A -benzodiazepine, serotonin, and neuropeptide ligands in the Mouse Defense Test Battery are reviewed. This review suggests that the Mouse Defense Test Battery is a sensitive and appropriate tool for preclinical evaluation of drugs potentially effective against defense-related disorders such as anxiety and panic. D

Section: Effects Of Selective 5-ht 1a Receptor Ligands In the Mouse Dmentioning

confidence: 98%

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

Griebel

European Journal of Pharmacology

2003

258

159

“…As noted above, buspirone has been FDA-approved for the treatment of anxiety, which led to the consideration of other azapirones ( 100 ). Gepirone, an azapirone and a selective 5-HT 1A receptor partial agonist, in its extended-release (ER) form, has been studied previously as an antidepressant, although it has been shown to have also anxiolytic properties ( 101 , 102 ). Gepirone ER is currently in Phase 2 trials for GAD, MDD, and hypoactive sexual desire disorder ( 103 ).…”

Section: Novel Treatments For Anxiety Disordersmentioning

confidence: 99%

Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options

et al. 2020

Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative dearth of novel medications under investigation for anxiety disorders. This review's first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha- and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Posttraumatic stress disorder and obsessive-compulsive disorder are excluded from this review. Second, we will review novel pharmacotherapeutic agents under investigation for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha- and beta-adrenergic agents, cannabinoids, and natural remedies. The outcome of the review reveals a lack of randomized double-blind placebo- controlled trials for anxiety disorders and few studies comparing novel treatments to existing anxiolytic agents. Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and larger-scale studies of promising agents with positive results from smaller trials.

Neuropsychopharmacology

“…The clinical significance of these studies is underscored by evidence that neuroendocrine and physiological responses to 5-HTIA agonists may be blunted in depressed patients (Lesch et al 1990a;Lesch et al 1990b;Cowen et al 1994;Moeller et al 1994;Mobayed and Dinan 1990). Several 5-HTIA agonists have also shown efficacy as antidepressants and anxiolytics (Cutler et al 1994;McGrath et al 1994;Pecknold et al 1993;Amsterdam 1992;Grof et al 1993;Heller et al 1990), and it has been proposed that many other antidepressants act by altering the sensitivity of hippocampal 5-HT 1 A receptors (Blier and de Montigny 1994;Stahl 1994).…”

mentioning

confidence: 99%

Effects of Antiglucocorticoid Treatment on 5-HT1A Function in Depressed Patients and Healthy Subjects

Price

1997

Clinical studies suggest that 5-HT1A receptor function may be blunted in depression, while 5-HT1A agonists may possess antidepressant activity. Preclinical findings implicate changes in 5-HT1A receptor sensitivity in the mechanism of antidepressant action. The hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in depression could be related to those observations, since 5-HT1A receptors are inhibited by glucocorticoids. To evaluate the interaction of the HPA and 5-HT1A systems, we pretreated 15 unipolar depressed patients and 12 healthy control subjects with the antiglucocorticoid ketoconazole (KTCZ) prior to administration of a test dose of the 5-HT1A agonist ipsapirone (IPS). Neuroendocrine (ACTH, cortisol, growth hormone), physiological (hypothermia), and behavioral responses to IPS were assessed. As expected, KTCZ inhibited cortisol biosynthesis, but non-HPA responses to IPS were not enhanced. This study failed to show that glucocorticoid modulation of 5-HT1A receptor function is altered in depression.