5,7-Dihydroxy-6-methoxy-4′-phenoxyflavone, a derivative of oroxylin A improves attention-deficit/hyperactivity disorder (ADHD)-like behaviors in spontaneously hypertensive rats

Ike C. Dela Peña, Seo Young Yoon, Yeni Kim, Haeil Park, Kyeong Man Kim, Jong Hoon Ryu, Chan Young Shin, Jae Hoon Cheong

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Oroxylin A, a major flavonoid in Scutellaria baicalensis, has been shown to alleviate attention-deficit/hyperactivity disorder (ADHD)-like behaviors in the spontaneously hypertensive rat (SHR) model of ADHD. As part of our continuing effort to discover effective ADHD drug candidates, we synthesized a number of oroxylin A derivatives and characterized their biological activities. Among all oroxylin A analogs, compound 7-7 (5,7-dihydroxy-6-methoxy-4′- phenoxyflavone) showed the most remarkable inhibition of dopamine reuptake alike methylphenidate, a dopamine transporter (DAT) blocker and typical drug for ADHD, and oroxylin A. It did not influence norepinephrine reuptake unlike atomoxetine, a selective norepinephrine inhibitor. Moreover, compound 7-7 reduced hyperactivity, sustained inattention and impulsivity in the SHR as measured by the open field, Y-maze and electro-foot shock aversive water drinking tests, respectively. Most drugs that enhance brain dopamine levels (e.g. DAT blockers like cocaine and methylphenidate) produce behavioral effects like those of stimulants causing them to be abused. However, the repeated treatment of compound 7-7 failed to elicit locomotor sensitization in rats, and neither produced conditioned place preference response nor maintained self-administration behavior. Altogether, the present study suggests the promising therapeutic value of compound 7-7 as an ADHD drug. Furthermore, compound 7-7 may be considered as an alternative therapy to psychostimulant ADHD treatments (e.g. amphetamine and methylphenidate) for which use has been deemed controversial due to their abuse liability.

Original languageEnglish
Pages (from-to)337-344
Number of pages8
JournalEuropean Journal of Pharmacology
Volume715
Issue number1-3
DOIs
StatePublished - 2013

Keywords

  • ADHD
  • Abuse potential
  • Oroxylin A derivative
  • SHR

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