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Characterization of 6-methoxyflavanone as a novel anxiolytic agent: A behavioral and pharmacokinetic approach.

Akbar, s, Subhan, F, Karim, N, Aman, U, Ullah, S, Shahid, M, Ahmad, N, Fawad, K and Sewell, Robert 2017. Characterization of 6-methoxyflavanone as a novel anxiolytic agent: A behavioral and pharmacokinetic approach. European Journal of Pharmacology 801 , pp. 19-27. 10.1016/j.ejphar.2017.02.047

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Abstract

Benzodiazepines are regularly prescribed for the treatment of anxiety though there are side effects. Flavonoids have selective affinity for GABAA receptors implicated in anxiolytic-like activity in rodents, but are devoid of the unwanted side effects of benzodiazepines. In this study, 6-methoxyflavanone (6-MeOF), a positive allosteric modulator of γ-amino butyric acid (GABA) responses at human recombinant GABAA receptors, was evaluated for its behavioral profile in the elevated plus-maze, as well as the staircase- and open-field tests in mice. In addition, the distribution of 6-MeOF in selected brain areas involved in anxiety (amygdala and cerebral cortex) was also examined using a validated high performance liquid chromatography/ultraviolet detection (HPLC/UV) method. 6-MeOF (10, 30 and 50 mg/kg) exerted an anxiolytic-like effect, increasing entries and time spent in the open arm and the central platform, as well as head-dipping frequency in the mouse elevated plus-maze assay. It also decreased rearing incidence without suppressing the number of steps ascended in the staircase test. Whereas, in the open-field anxiety test, 6-MeOF had no effect on locomotor activity at lower doses, a decrease was observed at the highest dose (100 mg/kg). 6-MeOF additionally produced an anxiolytic-like increase in the time spent at the center of the open-field apparatus. These effects were preferentially antagonized by pentylenetetrazole (15 mg/kg). Furthermore, pharmacokinetic studies disclosed a rapid appearance of 6-MeOF in the plasma and discrete brain areas. Taken together, our findings suggest that 6-MeOF readily crosses the blood brain barrier (BBB) generating anxiolytic activity, mediated through the GABAergic system.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Flavonoid; 6-Methoxyflavanone; anxiety; GABAA receptors; elevated plus-maze; staircase anxiety test
Publisher: Elsevier
ISSN: 0014-2999
Date of First Compliant Deposit: 22 October 2019
Date of Acceptance: 27 February 2017
Last Modified: 11 Mar 2020 03:15
URI: http://orca-mwe.cf.ac.uk/id/eprint/126191

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