New Melatonergic Agents

Melatonini sam ajorc hronobiologicalr egulatora ndh asb eenu sedf ort het reatmento fs leepp roblemsi n- cludingi nsomnia,�p arasomnia,�a ndc ircadianr hythms leepd isorders.�Be causeo fm elatonin'�s horth alf-life,� itss uitabilitya sad rugi sl imited.�Th us,�t hed evelopmento fp rolonged-releasem elatonina ndo therm elatoner- gicr eceptora gonistsw ithal ongerd urationo fa ctionw eren eeded.�R amelteon,�n on-indolicm elatonergica go- nisti st hefi rstd ruga pprovedi nt heU SAf ort het reatmento fi nsomnia.�I ts howedh ighlys electivem elatonin� MT1/MT2�r eceptora ffinitiesw hicha reb elievedt om ediatet hec ircadianr hythmw hereas,�n egligiblea ffinity � fort heM T3�r eceptora ndo therr eceptorsi nb rain.�Th iss electiver eceptora ffinitym aye xplaint hel acko fs ig- nificanta dversee ffecta ndl acko fd ependencyo rd ruga busep otential.�A nothern on-indolicm elatonergica go- nisti sa gomelatinei nitiallye valuatedf ori tsc hronobiotice ffect. �A fteri tss erotonergice ffectw asd iscovered,�i t� wasi nvestigateda sa na ntidepressant.�Th erea res tudiesi ndicatingu sefulnessi nc ontrollinga nxietyd isorder� andi ns easonala ffectived isorder.�S omes tudiess howeda gomelatineh asap otentialu sefulnessi ni mproving� sleepa rchitecture.�T asimelteoni sa lsoa nn on-indolicm elatonergica gonistw hichh ash igha ffinityf orb othM T1/ MT2�r eceptorsi nh umansa nds howedas imilara ffinityt om elatonin.�T IK-301,�a ni ndolicm elatonina nalogue� alsod isplaysah igha ffinityt owardsm elatoninM T1/MT2�r eceptors.�R ecently,�T IK-301�h asb eens hownt hati t� alsoa ctsa sa na ntagonisto ft hes erotoninr eceptors ubtype�5 -HT2Ba nd�5 -HT2c,�m orep otentt hana gomelatine.� Toe lucidatee fficacya nds afetyo fn ewlyd evelopedm elatonergicd rugs,�l ongert ermm ulticenterc linicalt ri- alsa ren eeded.� J Korean Sleep Res Soc 2011;8:25-30