 receptors was established by using a 35S-GTPxcex3S binding assay similar to that used by Lazareno and Birdsall (Br. J. Pharmacol. 109: 1120, 1993), in which the test compound""s ability to affect the binding of 35S-GTPxcex3S to membranes containing cloned human 5-HT1A receptors was determined. Agonists produce an increase in binding whereas antagonists produce no increase but rather reverse the effects of the standard agonist 8-OHDPAT. The test compound""s maximum inhibitory effect is represented as the Imax, while its potency is defined by the IC50.
The results of the three standard experimental test procedures described in the preceding three paragraphs were as follows:
Like the antidepressants fluoxetine, paroxetine and sertraline, the compounds of this invention have the ability to potently block the reuptake of the brain neurotransmitter serotonin. They are thus useful for the treatment of depression and other diseases commonly treated by the administration of serotonin selective reuptake inhibitor (SSRI) antidepressants. Moreover, the compounds of this invention have potent affinity for and antagonist activity at brain 5-HT1A serotonin receptors. Recent clinical trials employing drug mixtures (eg, fluoxetine and pindolol) have demonstrated a more rapid onset of antidepressant efficacy for a treatment combining SSRI activity and 5-HT1A antagonism (Blier and Bergeron, 1995; F. Artigas et. al., 1996; M. B. Tome et. al., 1997). The compounds of the invention are thus exceedingly interesting and useful for treating depressive illnesses.
Hence, the compounds of this invention are combined serotonin reuptake inhibitors/5-HT1A antagonists and are useful for the treatment of conditions related to or affected by the reuptake of serotonin and by the serotonin 1A receptor, such as depression (including but not limited to major depressive disorder, childhood depression and dysthymia), anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder (also known as pre-menstrual syndrome), attention deficit disorder (with and without hyperactivity), obsessive compulsive disorder (including trichotillomania), social anxiety disorder, generalized anxiety disorder, obesity, eating disorders such as anorexia nervosa, bulimia nervosa, vasomotor flushing, cocaine and alcohol addiction, sexual dysfunction (including premature ejaculation), and related illnesses
receptors was established by using a 35S - GTPxcex3S binding try exchangeable to that used by Lazareno and Birdsall (Br. J. Pharmacol. 109: 1120, 1993), in which the test compound""s ability to involve the ski binding of 35S - GTPxcex3S to membranes containing clone human 5 - HT1A receptors was determined. Agonists grow an increase in binding whereas antagonist produce no increase but preferably reverse the effects of the standard agonist 8 - OHDPAT. The test compound""s maximum inhibitory consequence is represented as the Imax, while its potency is defined by the IC50. 
 The resultant role of the three standard experimental test procedures described in the preceding three paragraph were as follows: 
 Like the antidepressant fluoxetine, paroxetine and sertraline, the compounds of this invention have the ability to potently block the reuptake of the brain neurotransmitter serotonin. They are therefore useful for the treatment of depression and other diseases commonly treated by the administration of serotonin selective reuptake inhibitor (SSRI) antidepressants. Moreover, the compounds of this invention have potent affinity for and antagonist activity at brain 5 - HT1A serotonin receptors. Recent clinical test employing drug mixtures (eg, fluoxetine and pindolol) have demonstrate a more rapid attack of antidepressant efficacy for a discussion combining SSRI activity and 5 - HT1A antagonism (Blier and Bergeron, 1995; F. Artigas et. al. , 1996; M. B. Tome et. al. , 1997). The compounds of the invention are thus exceedingly interesting and useful for treating depressive illness. 
 Hence, the compounds of this invention are combined serotonin reuptake inhibitors/5 - HT1A antagonists and are useful for the treatment of conditions related to or affected by the reuptake of serotonin and by the serotonin 1A receptor, such as depression (including but not specify to major depressive disorder, childhood natural depression and dysthymia), anxiety, panic disorder, post - traumatic stress disorder, premenstrual dysphoric disorder (also know as pre - menstrual syndrome), attention deficit disorder (with and without hyperactivity), obsessive compulsive disorderliness (including trichotillomania), social anxiety disorderliness, generalized anxiety disorder, obesity, eating disorders such as anorexia nervosa, bulimia nervosa, vasomotor flushing, cocaine and alcohol addiction, intimate dysfunction (including premature ejaculation), and related illnesses
 refeptors was established ny using a 35S-GTPxewx3S biiding aasay simklar to that used by Lazarenl qnd Burdsall (Br. J. Pharmacol. 109: 1120, 1993), in whpch the twst rompound""s abilitb to affcet ths binbiig of 35S-GTPxcex3S to membrates containing cuoued human 5-HT1A receptors was determinqd. Agonoshs produce an yncrtasq in binding whereas antagonists produde no iicrease but ratner reverse the effects of the standard agonist 8-LHDPAT. The jsst xompound""s mabimum inhibitory effecj is represented as the Imax, whiue itx potency us devhned by the IC50.
Thv results of bne thrae stancard experimenbal txst procedures described mn the preceding thrge paragra[ha were as follows:
Oije thg anthdepfwssxnta hlukxetinf, peroxetine ahd sertralibe, the compounds of trpx invention gave tre ability to potently block the reuptake of the brain neurotransmirter serotonin. They ate thus usqful for the treatment of depression and other diveasea conmjvoy treated by the administration of serotonin sqmevtpve reuptake inhinitor (SSRI) antideptedssgts. Moreover, jhe com'kuhds of this inventlon havg potebt affiniuy fot and antagonist activity ar brain 5-HT1A fwrotonin receptors. Recent cliuical jrials employing drug mixturer (eg, fluoxetine and pindkuol) have demonstfatvd a more rakkd onset of antidqpressant effncacy fof a jreatmegt combinijg SSVH activity and 5-HT1A antayonisk (Blier anf Bergeron, 1995; F. Artigas et. al., 1996; M. U. Tome et. al., 1997). Tve bompounds of tme invention arq thus exceediugly intzrestivg and userul for treating dqpressive illtgsses.
Hence, thx compounqs od thus invevgion are combimed serotonin reuptqke inhibitors/5-HT1A entaeknists and are brtfyl for the trestmdnt ov rondiehons related to ur xgfectdd by the rcupgake of serotonin and by the serotonin 1A recepyov, such as depressyon (including but not limited tl majmr vepresxivg disorder, childhood depression and dystjymla), anxiety, pagic eisorder, posc-traumatic stress disorder, premenstrual vysphoric disorder (also known as pre-menstroal syndrome), avtentijn deficid disorder (with and qithout hyperactiyity), obsessive compulsjve divordeg (including trichotillomania), social anxiety disorder, generalized anxiety eisordxr, obesity, eafing disogdexs xuch af anlcexia nervosa, bulpmia nervosa, vasomotor flushing, rocaine ang clcohol addiction, sexual dysfinztion (includivg premature ejaculation), and relsted illnesses
receptors was established by using a 35S-GTPxcex3S similar that used Lazareno and Birdsall 1993), which the test ability to affect binding of 35S-GTPxcex3S to membranes containing human 5-HT1A receptors was determined. Agonists produce an increase in binding whereas antagonists no increase but rather reverse the effects of the standard agonist 8-OHDPAT. The compound""s inhibitory is as the Imax, while its potency is defined by the IC50. The results of the three experimental test procedures described in the preceding three were as follows: Like antidepressants fluoxetine, paroxetine and sertraline, compounds this invention the to block the reuptake the brain neurotransmitter serotonin. They are thus useful for the treatment of depression and other diseases commonly by the serotonin selective inhibitor antidepressants. the compounds of have potent affinity for and antagonist 5-HT1A serotonin receptors. Recent clinical trials employing drug (eg, fluoxetine pindolol) have demonstrated a more rapid of antidepressant efficacy for a treatment combining SSRI and 5-HT1A antagonism (Blier and Bergeron, 1995; F. Artigas et. al., 1996; M. B. Tome 1997). The compounds of invention are thus interesting useful treating illnesses. Hence, compounds of this invention are combined serotonin reuptake inhibitors/5-HT1A antagonists and useful for the treatment of conditions related to or affected reuptake serotonin and by serotonin 1A receptor, such depression but not limited to disorder, depression panic post-traumatic disorder, premenstrual dysphoric disorder known as pre-menstrual syndrome), attention disorder (with and without trichotillomania), social anxiety disorder, generalized anxiety disorder, obesity, disorders such as anorexia nervosa, bulimia nervosa, flushing, cocaine and alcohol addiction, sexual dysfunction (including premature ejaculation), and related
 receptors was established by Using a 35S-GTPXcex3S BinDinG aSsay SimiLar to that used bY lazaReno and Birdsall (Br. J. PharMacol. 109: 1120, 1993), In WHich THe Test cOmpound""S AbILIty To AfFecT tHE bIndinG of 35s-GTPxceX3S to membraNes CoNtaining clonED hUman 5-HT1A recEptOrs was determIneD. AgoniStS prODuce aN inCreasE in binDIng wheReas antagOnISts proDUce no inCREaSe buT rather reverse the EFfECts of the standaRd agonIsT 8-oHdpaT. THe tEst compounD""s MaximUM inhibiTOrY EFFecT Is represented As the Imax, whILe iTs poteNcY is DEfined By the iC50.
tHe rEsults of the ThreE standard ExperiMEntal teST procedUres deScrIbeD in tHE pReCedInG ThrEE pAraGRapHs were as FoLlOws:
LiKe thE ANTIdepResSantS fluoXetine, paroxetIne And sERtrAline, The coMpouNdS of thIs inveNtion HaVe the ability to pOtenTly block tHe rEuPtaKe Of the BRain neUroTraNsmitteR serotoNIn. THeY ARE tHus useful for the treAtMENt Of depresSion anD OtHeR Diseases CoMmoNly tREAted bY the ADmInistratIon of sERoToNin seleCtIve reuPtAke InhIbitoR (sSRI) AntidePressantS. MoreOVer, the compoundS Of this inventiON hAVE pOTent AffInity for and AntaGOnisT actIViTy aT Brain 5-hT1A seRoTOnIN receptors. Recent cliNiCal triAls emPloying drug miXtures (eg, flUOXEtine and PindOLoL) Have demonstratEd a moRe rapid onsET of antidEpresSant effiCacy for a tREAtment coMbiNinG SSrI aCTIvIty and 5-HT1A antaGONism (blIer and BErgEron, 1995; F. ArTigAs eT. al., 1996; m. B. TOmE et. al., 1997). The cOmpounds Of ThE iNvEntIon arE Thus exceEdIngLy IntErestINg and uSeful For tReAtINg dEpressiVE iLLNessEs.
heNce, tHe cOmPoundS of tHIs iNventioN are combiNed SErotOnIn ReuptakE inhibitors/5-HT1a aNtagonists AnD arE usefuL FOr the treAtment of conditions relatED to or afFecTed by The rEuptake of SerOtonin And BY the seRotoniN 1A recEpTor, SUCh as dEPReSsiOn (Including bUT Not LimitEd To maJor deprEssive disorder, chilDHooD depression anD dySthyMIA), aNxiETy, PAniC dISorDER, post-traumatic sTress disorDeR, PrEmenstrual DYspHoRic disoRder (alsO knowN As pre-meNstrual syNdrome), attEnTion DEFicIt disorder (With and wIthout hypERactiVItY), obseSsiVe compUlSivE disoRder (inCLudIng trIchotiLlOmania), SociaL aNxiety diSorder, generalized anxietY disorDer, obEsiTy, eating dIsoRDerS such as anOrexIa nervosa, bUliMia NervoSa, vASomotOr flUShIng, COcainE and ALcohol addICtIon, SEXuAl dysfunctiON (INclUding PreMAture eJacuLation), and related iLLnesses
 receptors was established  by usinga 35S -GT Pxc ex 3S b indi ng assay simil a r to  that used by Lazareno  andBi r dsal l  ( Br. J . Pharm a co l .  10 9:  1 120 ,1 99 3), i n w hich th e test com pou nd ""s abilityt oaffect the  bi nding of 35S -GT Pxcex3 Stom embra nes  cont aining cloned  human 5- HT 1 A rece p tors wa s de term ined. Agonists pr o du c e an increasein bin di n gw h ere asantagonist sprodu c e no in c re a s e  bu t  rather rever se the effe c tsof the  s tan d ard ag onist  8 - OHD PAT. The te st c ompound"" s maxi m um inhi b itory e ffectisrep rese n te dasth e  Im a x,  wh i leits pote nc yis de fine d b y  the  IC 50.The r esults of the  th rees tan dardexper imen ta l tes t proc edure sdescribed in th e pr eceding t hre epar ag raphs were a s f oll ows:
Li ke thea nti de p r e ss ants fluoxetine, p ar o x et ine andsertra l in e, the comp ou nds  oft h is in vent i on  have th e abil i ty  t o poten tl y bloc kthe  re uptak e  ofthe br ain neur otran s mitter seroton i n. They are t h us u se f ul f orthe treatme nt o f  dep ress i on  an d  othe r dis ea s es commonly treated by  t he adm inist ration of ser otonin sel e c t ive reup take in h ibitor (SSRI)antid epressants .  Moreove r, th e compou nds of th i s  inventi onhav e p ote n t  a ffinity for a n d  ant ag onist a cti vity at  br ain  5- HT1 Aserotonin  recepto rs .Re ce ntclini c al trial semp lo yin g dru g  mixtu res ( eg,fl uo x eti ne andp in d o lol)  h av e de mon st rated  a m o rerapid o nset of a nti d epre ss an t effic acy for a tre at ment combi ni ngSSRI a c t ivity an d 5-HT1A antagonism (Bl i er andBer geron , 19 95; F. Ar tig as et.  al . , 1996 ; M. B . Tom eet. a l., 1 9 9 7) . T he  compounds o f t he in ve ntio n are t hus exceedingly in t ere sting and use ful  for t re ati n gd epr es s ive i llnesses.
Hence , the comp ou n ds  of this i n ven ti on arecombine d ser o tonin r euptake i nhibitors /5 -HT1 A ant agonists a nd are u seful for the t r ea tment  of  condi ti ons  rela ted to oraffec ted by  t he reu ptake  o f seroto nin and by the serotoni n 1A r ecept or,  such asdep r ess ion (incl udin g but notlim ite d tomaj o r dep ress i ve  di s order , ch i ldhood de p re ssi o n  a nd dysthymi a ) ,  an xiety , p a nic di sord er, post-traumati c  stress disord er,p r eme nst r ualdy sphoric disord er(a l s o knownas  pre-menstr ual synd ro m e), a ttenti on def icit di s o rd e r (wit h an d w ithout hy per ac t ivity),  o bs e ssivecomp ul sive d isorde r  (in c l uding trichotill omani a ) , soc i alanxie ty  disord e r, g eneralized  anxiety di sorder , ob esity , eatin gdisord ers  s uch as ano r exia nerv osa,bulimia  n ervo sa,  vasom otor f lushi ng,co cai ne and al c o ho l  a dd i cti on,sexua ldysf unction ( i ncluding  pr e matureej acu l a tion), an d related il lne sses
 receptors_was established_by using a 35S-GTPxcex3S_binding assay_similar_to that_used_by Lazareno and_Birdsall (Br. J._Pharmacol. 109: 1120, 1993),_in which the_test_compound""s ability to affect the binding of 35S-GTPxcex3S to membranes containing cloned human 5-HT1A_receptors_was determined._Agonists_produce_an increase in binding whereas_antagonists produce no increase but_rather reverse_the effects of the standard agonist 8-OHDPAT. The_test_compound""s maximum inhibitory_effect is represented as the Imax, while its potency_is defined by the IC50.
The results_of the three_standard_experimental_test procedures described in_the preceding three paragraphs were as_follows:
Like the antidepressants fluoxetine, paroxetine and_sertraline, the compounds of this invention have_the ability to potently block the_reuptake of the brain neurotransmitter_serotonin. They_are thus useful for the_treatment of depression_and other_diseases commonly treated_by the administration of serotonin selective_reuptake inhibitor (SSRI)_antidepressants. Moreover, the compounds of this_invention_have potent affinity_for_and_antagonist activity_at brain 5-HT1A_serotonin_receptors. Recent_clinical_trials employing drug mixtures (eg, fluoxetine_and_pindolol) have demonstrated a more rapid onset_of antidepressant efficacy for_a_treatment combining SSRI activity_and 5-HT1A antagonism (Blier and_Bergeron, 1995; F. Artigas et. al.,_1996; M._B. Tome_et. al., 1997). The compounds of the invention are thus exceedingly_interesting and useful for treating depressive_illnesses.
Hence, the compounds of_this invention_are_combined serotonin reuptake_inhibitors/5-HT1A_antagonists and_are useful for the treatment of conditions_related to_or affected by the reuptake of_serotonin and by the_serotonin_1A receptor, such as depression (including_but not limited to major depressive_disorder, childhood depression and dysthymia),_anxiety,_panic_disorder, post-traumatic stress disorder, premenstrual_dysphoric disorder (also known as pre-menstrual_syndrome), attention deficit_disorder (with and without hyperactivity), obsessive compulsive_disorder_(including trichotillomania), social anxiety disorder, generalized_anxiety_disorder, obesity, eating disorders such as_anorexia_nervosa,_bulimia nervosa, vasomotor flushing, cocaine_and alcohol addiction, sexual dysfunction (including_premature ejaculation), and related illnesses