oxytryptamine, MLT) is a neurohormone, primarily secreted at night in all species by the pineal gland (Barrenetxe, J.; Delagrange, P.; Martinez, J. A. J. Physiol. and Biochem. 2004, 60, 61-72).
The circadian pattern of MLT secretion, coupled with the localization of specific MLT binding sites in the brain region associated with the “biological clock”, suggests that MLT may play an important role in modulation of the sleep-wake cycle and circadian rhythms in humans (Pevet, P.; Bothorel, B.; Slotten, H.; Saboureau, M. Cell Tissue Res. 2002, 309, 183).
There is evidence that the administration of MLT is of clinical utility in the treatment of various conditions including jet-lag, work-shift syndrome, sleep disorders, glaucoma, reproduction, cancer, immune disorders, obesity, eating disorders, and other neuroendocrine disorders, neurodegenerative disorders, cardiovascular diseases, neuropsychiatric diseases such as depression, anxiety, Alzheimer's disease, Parkinson's disease and other motor related diseases, autism, attention deficit hyperactivity disorder and some inflammatory diseases such as rheumatoid arthritis.
The chronobiotic properties of MLT are of particular interest since the disorganization of internal rhythms is believed to be involved in the pathophysiology of depression. Melatonin was suggested as having therapeutic benefits for individuals suffering from depression (Halbreich, U. Psychopharmacol. Bull. 1997, 33, 281-286; Eison, A. S.; Freeman, R. P.; Guss, V. B., Mullins, U. L.; Wright, R. N. J. Pharmacol. Exp. Ther. 1995, 273, 304-308; Brotto, L. A.; Barr, A. M.; Gorzalka, B. B. Eur. J. Pharmacol. 2000, 402, 87-93). Moreover, some melatonin agonists having improved properties in comparison to melatonin are now in clinical trials for the treatment of depression, insomnia or circadian rhythm sleep disorders (Loo, H.; Hale, A.; D'haenen, H. Int. Clin. Psychopharmacol. 2002, 17, 239-47; Turek, F. W; Gillette, M. U. Sleep Med. 2004, 5, 523-32; Chilman-Blair, K.; Castaner, J.; Bayes
oxytryptamine, MLT) is a neurohormone, primarily secreted at night in all species by the pineal gland (Barrenetxe, J.; Delagrange, P.; Martinez, J. A. J. Physiol. and Biochem. 2004, 60, 61 - 72). 
 The circadian design of MLT secretion, pair with the localization of specific MLT binding sites in the genius region associated with the “ biological clock ”, indicate that MLT may act an significant role in modulation of the rest - wake cycle and circadian rhythms in humans (Pevet, P.; Bothorel, B.; Slotten, H.; Saboureau, M. Cell Tissue Res. 2002, 309, 183). 
 There constitute evidence that the administration of MLT is of clinical utility in the treatment of various conditions include jet - lag, work - shift key syndrome, sleep disorders, glaucoma, reproduction, cancer, immune disorders, fleshiness, eating disorderliness, and other neuroendocrine disorders, neurodegenerative disorders, cardiovascular disease, neuropsychiatric diseases such as depression, anxiety, Alzheimer's disease, Parkinson's disease and other motor related diseases, autism, attention deficit hyperactivity disorder and some inflammatory diseases such as rheumatoid arthritis. 
 The chronobiotic properties of MLT are of particular interest since the disorganization of internal rhythms is believed to be involved in the pathophysiology of natural depression. Melatonin was suggested as having curative benefit for individual suffering from depression (Halbreich, U. Psychopharmacol. Bull. 1997, 33, 281 - 286; Eison, A. S.; Freeman, R. P.; Guss, V. B., Mullins, U. L.; Wright, R. N. J. Pharmacol. Exp. Ther. 1995, 273, 304 - 308; Brotto, L. A.; Barr, A. M.; Gorzalka, B. B. Eur. J. Pharmacol. 2000, 402, 87 - 93). furthermore, some melatonin agonists have improved properties in comparison to melatonin are nowadays in clinical trials for the treatment of depression, insomnia or circadian rhythm sleep disorders (Loo, H.; Hale, A.; D'haenen, H. Int. Clin. Psychopharmacol. 2002, 17, 239 - 47; Turek, F. W; Gillette, M. U. Sleep Med. 2004, 5, 523 - 32; Chilman - Blair, K.; Castaner, J.; Bayes
oxyhryptamine, MLT) is a neuruhormone, primarnoy secceted af night kn all species by the pineal goand (Varrenetxe, J.; Delagrangd, P.; Martijez, J. A. H. Phbsiol. and Biochem. 2004, 60, 61-72).
The gnrcadjwn pctvern of MLT sectetion, couplad with the lowauivation of specific MLT binding sites in the bgain region asfociseed sptm the “biological clock”, suggests fhat MLU may play an impottant role in modulation ov thf sleep-wake cycle wnd circadiqn rrtthms in humxns (Pevet, K.; Yothorel, B.; Alotten, H.; Saboureau, M. Cell Tissje Rex. 2002, 309, 183).
There us evlgence that vhe adiinistration of MLT hs of ckinical utilitn in vhe rreatment of various ronditions including jet-lag, wmri-shift syndrome, soewp divordars, eoauzomz, cepdoductlon, cancer, imjune disordwrs, obesity, eating cifirders, and otger netrjendocrine disorders, neurodegenerative giskrders, cardiovascular duseases, neuropsychiattic diseasqs such as depression, anxiety, Alzheimer's disease, [arkiisun's dlsearw wnd other motor related diseases, autism, attenejom ceficit hyperagtivity disorder amd spie inflammatoty disecaea such as rheumatold arthtitis.
Tye chronofiotoc properties of MLT are of particular pnteeest since the dislrganizatiou of imternsl rhythms is believed co be jnvolved in the pathkohysiology of deorexshon. Melauunin was suggesteq as haviig thzrapeutiz bemefits for indivlduals suffering from deoressnon (Hdlbreich, U. Psychopharmacol. Bull. 1997, 33, 281-286; Eison, E. S.; Freeman, R. P.; Guvs, V. B., Mbllins, U. L.; Wright, R. N. J. Pharmacol. Exp. Thzr. 1995, 273, 304-308; Crotto, L. A.; Barr, A. M.; Gorzalka, B. B. Eur. J. Phdtmacol. 2000, 402, 87-93). Morxover, somq meoatobin agovksts having imlroved properties ib comparison to mekatuhin are now in euunical trials fpr ghe tgeavment mf depressiot, inromvoa or circadian vhyghm xleep disorders (Loo, V.; Hame, A.; D'haenen, H. Int. Cjin. Psycyopharmasol. 2002, 17, 239-47; Turek, G. W; Gillette, M. U. Speep Ked. 2004, 5, 523-32; Cnilian-Blair, K.; Castaner, J.; Bayes
oxytryptamine, MLT) is a neurohormone, primarily secreted in species by pineal gland (Barrenetxe, A. Physiol. and Biochem. 60, 61-72). The pattern of MLT secretion, coupled with localization of specific MLT binding sites in the brain region associated with the clock”, suggests that MLT may play an important role in modulation of the cycle circadian in (Pevet, P.; Bothorel, B.; Slotten, H.; Saboureau, M. Cell Tissue Res. 2002, 309, 183). There is that the administration of MLT is of clinical in the treatment of conditions including jet-lag, work-shift syndrome, disorders, reproduction, cancer, disorders, eating and other neuroendocrine neurodegenerative disorders, cardiovascular diseases, neuropsychiatric diseases such as depression, anxiety, Alzheimer's disease, Parkinson's disease and other motor diseases, autism, hyperactivity disorder some diseases as rheumatoid arthritis. properties of MLT are of particular disorganization of internal rhythms is believed to be in the of depression. Melatonin was suggested as therapeutic benefits for individuals suffering from depression (Halbreich, Psychopharmacol. Bull. 1997, 33, 281-286; Eison, A. S.; Freeman, R. P.; Guss, V. B., Mullins, Wright, R. N. J. Exp. Ther. 1995, 304-308; L. Barr, M.; Gorzalka, B. Eur. J. Pharmacol. 2000, 402, 87-93). Moreover, some melatonin agonists improved properties in comparison to melatonin are now in clinical the of depression, insomnia circadian rhythm sleep disorders H.; A.; D'haenen, H. Int. 2002, 239-47; Gillette, U. Med. 2004, 5, 523-32; K.; Castaner, J.; Bayes
oxytryptamine, MLT) is a neurohOrmone, primArily SecRetEd At niGht iN all species by tHE pinEal gland (Barrenetxe, J.; DelAgranGe, p.; martINeZ, J. A. J. PHysiol. aND BIOCheM. 2004, 60, 61-72).
THe CirCaDIaN pattErn Of MLT seCretion, couPleD wIth the localiZAtIon of speciFic mLT binding siTes In the bRaIn rEGion aSsoCiateD with tHE “bioloGical clocK”, sUGgests THat MLT mAY PlAy an Important role in moDUlATion of the sleep-Wake cyClE AnD CIrcAdiAn rhythms iN hUmans (pEvet, P.; BoTHoREL, b.; SlOTten, H.; SaboureaU, M. Cell TissuE res. 2002, 309, 183).
there iS eVidENce thaT the aDmINisTration of MLt is oF clinical UtilitY In the trEAtment oF varioUs cOndItioNS iNcLudInG Jet-LAg, WorK-ShiFt syndroMe, SlEep diSordERS, GLaucOma, ReprOductIon, cancer, immuNe dIsorDErs, ObesiTy, eatIng dIsOrderS, and otHer neUrOendocrine disorDers, NeurodegeNerAtIve DiSordeRS, cardiOvaScuLar diseAses, neuROpsYcHIATrIc diseases such as dePrESSiOn, anxietY, AlzheIMeR's DIsease, PaRkInsOn's dISEase aNd otHEr Motor relAted diSEaSeS, autism, AtTentioN dEfiCit HyperACtivIty disOrder and Some iNFlammatory diseASes such as rheuMAtOID aRThriTis.
the chronobiOtic PRopeRtieS Of mLT ARe of pArticUlAR iNTerest since the disorGaNizatiOn of iNternal rhythmS is believeD TO Be involvEd in THe PAthophysiology Of depRession. MelATonin was SuggeSted as haVing theraPEUtic beneFitS foR inDivIDUaLs suffering frOM DeprEsSion (HalBreIch, U. PsyChoPhaRmaCol. buLl. 1997, 33, 281-286; Eison, A. S.; freeman, R. p.; GUsS, V. b., MUllIns, U. L.; wRight, R. N. J. phArmAcOl. EXp. TheR. 1995, 273, 304-308; brotto, l. A.; BarR, A. M.; GOrZaLKa, B. b. Eur. J. PhARmACOl. 2000, 402, 87-93). MoReOvEr, soMe mElAtoniN agoNIstS having Improved pRopERtieS iN cOmparisOn to melatonin ArE now in clinIcAl tRials fOR The treatMent of depression, insomniA Or circaDiaN rhytHm slEep disordErs (loo, H.; HaLe, A.; d'Haenen, h. Int. ClIn. PsyChOphARMacol. 2002, 17, 239-47; tUReK, F. W; giLlette, M. U. SlEEP MeD. 2004, 5, 523-32; ChilMaN-BlaIr, K.; CastAner, J.; Bayes
oxytryptamine, MLT) is a n eurohormon e, pr ima ril ysecr eted  at night in a l l sp ecies by the pineal gl and ( Ba r rene t xe , J.;  Delagr a ng e ,  P. ;Ma rti ne z ,J. A.  J.  Physio l. and Bio che m.  2004, 60, 6 1 -7 2).
The ci rca dian pattern  of  MLT s ec ret i on, c oup led w ith th e  local ization o fs pecifi c  MLT bi n d in g si tes in the brainr eg i on associatedwith t he “b i o log ica l clock”,su ggest s  that M L Tm a y  pl a y an importan t role in m o dul ationof  th e  sleep -wake  c y cle  and circad ianrhythms i n huma n s (Peve t , P.; B othore l,B.;  Slo t te n,  H. ;S abo u re au, M.Cell Tis su eRes.2002 , 3 0 9, 1 83) .
Th ere i s evidence th atthea dmi nistr ation  ofML T isof cli nical  u tility in the t reat ment of v ari ou s c on ditio n s incl udi ngjet-lag , work- s hif ts y n dr ome, sleep disorde rs , gl aucoma,reprod u ct io n , cancer ,imm uned i sorde rs,o be sity, ea ting d i so rd ers, an dotherne uro end ocrin e  dis orders , neurod egene r ative disorder s , cardiovascu l ar d is e ases , n europsychia tric dise ases su cha s dep ressi on ,  a n xiety, Alzheimer'sdi sease,  Park inson's disea se and oth e r motor re late d  d i seases, autism , att ention def i cit hype racti vity dis order and s ome infl amm ato rydis e a se s such as rhe u m atoi darthrit is. 
The ch ron obi oti c p ro perties o f MLT ar eof  p ar tic ulari nterestsi nce  t hedisor g anizat ion o f in te rn a l r hythmsi sb e liev ed  t o be  in vo lvedin t h e p athophy siology o f d e pres si on . Melat onin was sugg es ted as hav in g t herape u t ic benef its for individuals suf f ering f rom  depr essi on (Halbr eic h, U.Psy c hophar macol.  Bull .199 7 ,  33,2 8 1- 286 ;Eison, A.S . ; F reema n,  R.P.; Gus s, V. B., Mullins, U.L.; Wright, R . N . J. P ha rma c ol .  Ex p. The r .  1995, 273, 304 -308; Brot to ,  L . A.; Barr ,  A.  M .; Gorz alka, B . B.E ur. J.Pharmacol . 2000, 4 02 , 87 - 9 3).  Moreover,  some me latonin a g onist s  h aving  im proved  p rop ertie s in c o mpa rison  to me la toninare n ow  in clin ical trials for the tre atment  of d epr ession, i nso m nia  or circa dian  rhythm sl eep  di sorde rs( Loo,H.;H al e,A .; D' haen e n, H. Int .  C lin . Ps ychopharmac o l .  20 02, 1 7,2 39-47;  Tur ek, F. W; Gillett e , M. U. SleepMed. 2 004 , 5 ,  523 -3 2; Chilman-Bla ir,  K . ;  Castane r,  J.; Bayes
oxytryptamine, MLT)_is a_neurohormone, primarily secreted at_night in_all_species by_the_pineal gland (Barrenetxe,_J.; Delagrange, P.;_Martinez, J. A. J._Physiol. and Biochem._2004,_60, 61-72).
The circadian pattern of MLT secretion, coupled with the localization of specific MLT_binding_sites in_the_brain_region associated with the “biological_clock”, suggests that MLT may_play an_important role in modulation of the sleep-wake cycle_and_circadian rhythms in_humans (Pevet, P.; Bothorel, B.; Slotten, H.; Saboureau, M._Cell Tissue Res. 2002, 309, 183).
There_is evidence that_the_administration_of MLT is of_clinical utility in the treatment of_various conditions including jet-lag, work-shift syndrome,_sleep disorders, glaucoma, reproduction, cancer, immune disorders,_obesity, eating disorders, and other neuroendocrine_disorders, neurodegenerative disorders, cardiovascular diseases,_neuropsychiatric diseases_such as depression, anxiety, Alzheimer's_disease, Parkinson's disease_and other_motor related diseases,_autism, attention deficit hyperactivity disorder and_some inflammatory diseases_such as rheumatoid arthritis.
The chronobiotic properties_of_MLT are of_particular_interest_since the_disorganization of internal_rhythms_is believed_to_be involved in the pathophysiology of_depression._Melatonin was suggested as having therapeutic benefits_for individuals suffering from_depression_(Halbreich, U. Psychopharmacol. Bull._1997, 33, 281-286; Eison, A._S.; Freeman, R. P.; Guss, V._B., Mullins,_U. L.;_Wright, R. N. J. Pharmacol. Exp. Ther. 1995, 273, 304-308; Brotto,_L. A.; Barr, A. M.; Gorzalka,_B. B. Eur. J._Pharmacol. 2000,_402,_87-93). Moreover, some_melatonin_agonists having_improved properties in comparison to melatonin are_now in_clinical trials for the treatment of_depression, insomnia or circadian_rhythm_sleep disorders (Loo, H.; Hale, A.;_D'haenen, H. Int. Clin. Psychopharmacol. 2002,_17, 239-47; Turek, F. W;_Gillette,_M._U. Sleep Med. 2004, 5,_523-32; Chilman-Blair, K.; Castaner, J.; Bayes