OBJECTIVE Bisbenzylisoquinoline(BBI)alkaloids have extensive pharmacological functions.The aim of this study was to investigate the mechanisms underlying the antidepressant-like action of 7-O-ethylfangchinoline(YH-200...OBJECTIVE Bisbenzylisoquinoline(BBI)alkaloids have extensive pharmacological functions.The aim of this study was to investigate the mechanisms underlying the antidepressant-like action of 7-O-ethylfangchinoline(YH-200)in mice.METHODS Male ICR mice were used in the forced swimming(FST)and tail suspension tests(TST).RESULTS YH-200(60mg·kg-1,ig)decreased the immobility time in FST and TST,and prolonged the latency to immobility in FST.YH-200 revealed more potent anti-immobility activity than its BBI derivative tetrandrine.In addition,the pretreatment of mice with prazosin(1mg·kg-1,ip,anα1-adrenoceptor antagonist),propranolol(2 mg·kg-1,ip,a nonselectiveβ-adrenoceptor antagonist),SCH23390(0.05mg·kg-1,ip,a dopamine D1/D5 receptor antagonist),haloperidol(0.2mg·kg-1,ip,a dopamine D2/D3 receptor antagonist)and NBQX(10mg·kg-1,ip,an AMPA receptor antagonist)prevented the antidepressant-like effect of YH-200(60mg·kg-1,ig)in FST.Besides that,the pretreatment of mice with yohimbine(1mg·kg-1,ip,an α2 adrenoceptor antagonist)augmented the antidepressant-like effect of YH-200(30mg·kg-1,ig)in FST.After 14 dadministration,YH-200(30 and 60mg·kg-1,ig)did not develop drug resistance,but the potency was strengthened,meanwhile,it did not influence the changes in mice body weight.CONCLUSION YH-200 may possess the therapeutic potential for the treatment of depression via the multi-targets including the noradrenergic(α1,α2 and β-adrenoceptors),dopaminergic(D1/D5 and D2/D3receptors)and AMPAergic systems.展开更多
基金The project supported by National Natural Science Foundation of China(81173031,81202511 and81302746)
文摘OBJECTIVE Bisbenzylisoquinoline(BBI)alkaloids have extensive pharmacological functions.The aim of this study was to investigate the mechanisms underlying the antidepressant-like action of 7-O-ethylfangchinoline(YH-200)in mice.METHODS Male ICR mice were used in the forced swimming(FST)and tail suspension tests(TST).RESULTS YH-200(60mg·kg-1,ig)decreased the immobility time in FST and TST,and prolonged the latency to immobility in FST.YH-200 revealed more potent anti-immobility activity than its BBI derivative tetrandrine.In addition,the pretreatment of mice with prazosin(1mg·kg-1,ip,anα1-adrenoceptor antagonist),propranolol(2 mg·kg-1,ip,a nonselectiveβ-adrenoceptor antagonist),SCH23390(0.05mg·kg-1,ip,a dopamine D1/D5 receptor antagonist),haloperidol(0.2mg·kg-1,ip,a dopamine D2/D3 receptor antagonist)and NBQX(10mg·kg-1,ip,an AMPA receptor antagonist)prevented the antidepressant-like effect of YH-200(60mg·kg-1,ig)in FST.Besides that,the pretreatment of mice with yohimbine(1mg·kg-1,ip,an α2 adrenoceptor antagonist)augmented the antidepressant-like effect of YH-200(30mg·kg-1,ig)in FST.After 14 dadministration,YH-200(30 and 60mg·kg-1,ig)did not develop drug resistance,but the potency was strengthened,meanwhile,it did not influence the changes in mice body weight.CONCLUSION YH-200 may possess the therapeutic potential for the treatment of depression via the multi-targets including the noradrenergic(α1,α2 and β-adrenoceptors),dopaminergic(D1/D5 and D2/D3receptors)and AMPAergic systems.
