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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.
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 decreased (FST) and tail suspension tests (TST) .RESULTS YH-200 (60 mg · 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 (1 mg · kg -1, ip, an α1-adrenoceptor antagonist), propranolol (2 mg · kg -1, ip, a nonselective β-adrenoceptor antagonist) , SCH23390 (0.05 mg · kg -1, ip, a dopamine D1 / D5 receptor antagonist), haloperidol (0.2 mg · kg -1, ip, a dopamine D2 / D3 receptor antagonist) and NBQX , an AMPA receptor antagonist prevented the antidepressant-like effect of YH-200 (60 mg · kg-1, ig) in FST.Besides that, the pretreatment of mice with yohimbine (1 mg · kg- 1, ip, an α2 adrenoceptor antagonist augmented the antidepressant-like effect of YH-200 (30 mg · kg-1, ig) in FST. After 14 dadministration, 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 / D3 receptors) and AMPAergic systems.