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

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

  • Eur J Pharmacol. 2017 Apr 15:801:19-27. doi: 10.1016/j.ejphar.2017.02.047.
Shehla Akbar 1,  Fazal Subhan 2,  Nasiara Karim 3,  Urooj Aman 4,  Sami Ullah 5,  Muhammad Shahid 6,  Nisar Ahmad 7,  Khwaja Fawad 8,  Robert D E Sewell 9
Affiliations

Affiliations

  • 1 Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. Electronic address: [email protected].
  • 2 Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. Electronic address: [email protected].
  • 3 Department of Pharmacy, University of Malakand, Chakdara, Pakistan. Electronic address: [email protected].
  • 4 Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. Electronic address: [email protected].
  • 5 Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. Electronic address: [email protected].
  • 6 Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. Electronic address: [email protected].
  • 7 Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. Electronic address: [email protected].
  • 8 Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. Electronic address: [email protected].
  • 9 Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UK. Electronic address: [email protected].
PMID: 28257822 DOI: 10.1016/j.ejphar.2017.02.047
Abstract

Benzodiazepines are regularly prescribed for 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- plus 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 50mg/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 (100mg/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 (15mg/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.

Keywords

6-Methoxyflavanone; 6-Methoxyflavanone (PubChem CID: 97860); Flavonoid; GABA(A) receptors; anxiety; elevated plus-maze; staircase anxiety test.

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