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. 2007 Dec 7;13(4):475–501. doi: 10.1111/j.1527-3458.2007.00025.x

Pharmacology of the β‐Carboline FG‐7142, a Partial Inverse Agonist at the Benzodiazepine Allosteric Site of the GABAA Receptor: Neurochemical, Neurophysiological, and Behavioral Effects

Andrew K Evans 1, Christopher A Lowry 1
PMCID: PMC6494137  PMID: 18078430

ABSTRACT

Given the well‐established role of benzodiazepines in treating anxiety disorders, β‐carbolines, spanning a spectrum from full agonists to full inverse agonists at the benzodiazepine allosteric site for the GABAA receptor, can provide valuable insight into the neural mechanisms underlying anxiety‐related physiology and behavior. FG‐7142 is a partial inverse agonist at the benzodiazepine allosteric site with its highest affinity for the α1 subunit‐containing GABAA receptor, although it is not selective. FG‐7142 also has its highest efficacy for modulation of GABA‐induced chloride flux mediated at the α1 subunit‐containing GABAA receptor. FG‐7142 activates a recognized anxiety‐related neural network and interacts with serotonergic, dopaminergic, cholinergic, and noradrenergic modulatory systems within that network. FG‐7142 has been shown to induce anxiety‐related behavioral and physiological responses in a variety of experimental paradigms across numerous mammalian and non‐mammalian species, including humans. FG‐7142 has proconflict actions across anxiety‐related behavioral paradigms, modulates attentional processes, and increases cardioacceleratory sympathetic reactivity and neuroendocrine reactivity. Both acute and chronic FG‐7142 treatment are proconvulsive, upregulate cortical adrenoreceptors, decrease subsequent actions of GABA and β‐carboline agonists, and increase the effectiveness of subsequent GABAA receptor antagonists and β‐carboline inverse agonists. FG‐7142, as a partial inverse agonist, can help to elucidate individual components of full agonism of benzodiazepine binding sites and may serve to identify the specific GABAA receptor subtypes involved in specific behavioral and physiological responses.

Keywords: Anxiety, Benzodiazepine binding site, Carbolines, FG‐7142, GABAA receptors

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The authors have no conflict of interest.

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