TY - JOUR
T1 - 5,7-Dihydroxy-6-methoxy-4′-phenoxyflavone, a derivative of oroxylin A improves attention-deficit/hyperactivity disorder (ADHD)-like behaviors in spontaneously hypertensive rats
AU - Dela Peña, Ike C.
AU - Yoon, Seo Young
AU - Kim, Yeni
AU - Park, Haeil
AU - Kim, Kyeong Man
AU - Ryu, Jong Hoon
AU - Shin, Chan Young
AU - Cheong, Jae Hoon
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - ADHD
KW - Abuse potential
KW - Oroxylin A derivative
KW - SHR
UR - http://www.scopus.com/inward/record.url?scp=84885483249&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2013.05.002
DO - 10.1016/j.ejphar.2013.05.002
M3 - Article
C2 - 23707903
AN - SCOPUS:84885483249
SN - 0014-2999
VL - 715
SP - 337
EP - 344
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -