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(21) Ellenbroek, B. A.; Lieg
́
eois, J.-F.; Bruhwyler, J.; Cools, A. R. The
clozapine. III. Replacement of the tricyclic nucleus with a bicyclic
template. Aust. J. Chem. 2007, 60, 928−933.
effects of JL13, a pyridobenzoxazepine with potential atypical
antipsychotic activity, in animal models for schizophrenia. J. Pharmacol.
Exp. Ther. 2001, 298, 386−391.
(38) Capuano, B.; Crosby, I. T.; Lloyd, E. J.; Neve, J. E.; Taylor, D. A.
Aminimides as potential CNS acting agents. II. Design, synthesis, and
receptor binding of 4′-arylalkyl aminimide analogues of clozapine as
prospective novel antipsychotics. Aust. J. Chem. 2008, 60, 5−10.
(39) Capuano, B.; Crosby, I. T.; Lloyd, E. J.; Podloucka, A.; Taylor,
D. A. Synthesis and preliminary pharmacological evaluation of 4′-
arylalkyl analogues of clozapine. IV. The effects of aromaticity and
isosteric replacement. Aust. J. Chem. 2008, 60, 930−940.
(22) Bruhwyler, J.; Lieg
Taylor, A.; Meltzer, H. Y.; Delarge, J.; Gec
́
eois, J.-F.; Bergman, J.; Carey, G.; Goudie, A.;
zy, J. JL13, a
́
pyridobenzoxazepine compound with potential atypical antipsychotic
activity: A review of its behavioural properties. Pharmacol. Res. 1997,
36, 255−264.
́ ́
(23) Casey, D. E.; Bruhwyler, J.; Delarge, J.; Geczy, J.; Liegeois, J.-F.
The behavioral effects of acute and chronic JL13, a putative
antipsychotic, in Cebus non-human primates. Psychopharmacology
2001, 157, 228−235.
(40) Li, Z.; Huang, M.; Ichikawa, J.; Dai, J.; Meltzer, H. Y. N-
Desmethylclozapine, a major metabolite of clozapine, increases cortical
acetylcholine and dopamine release in vivo via stimulation of M1
muscarinic receptors. Neuropsychopharmacology 2005, 30, 1986−1995.
(41) Prus, A. J.; Pehrson, A. L.; Philibin, S. D.; Wood, J. T.; Vunck, S.
A.; Porter, J. H. The role of M1 muscarinic cholinergic receptors in the
discriminative stimulus properties of N-desmethylclozapine and the
atypical antipsychotic drug clozapine in rats. Psychopharmacology
(Berlin) 2009, 203, 295−301.
(42) Apiquian, R.; Ulloa, E.; Fresan, A.; Loyzaga, C.; Nicolini, H.;
Kapur, S. Amoxapine shows atypical antipsychotic effects in paptients
with schizophrenia: results from a prospective open-label study.
Schizophr. Res. 2003, 59, 35−39.
(43) Jensen, N. H.; Rodriguiz, R. M.; Caron, M. G.; Wetsel, W. C.;
Rothman, R. B.; Roth, B. L. N-desalkylquetiapine, a potent
norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a
putative mediator of quetiapine’s antidepressant activity. Neuro-
psychopharmacology 2008, 33, 2303−2312.
(44) Shobo, M.; Kondo, Y.; Yamada, H.; Mihara, T.; Yamamoto, N.;
Katsuoka, M.; Harada, K.; Ni, K.; Matsuoka, N. Norzotepine, a major
metabolite of zotepine, exerts atypical antipsychotic-like and
antidepressant-like actions through its potent inhibition of norepi-
nephrine reuptake. J. Pharmacol. Exp. Ther. 2010, 333, 772−781.
(45) Lamy, C. Synthesis, evaluation and psychopharmacological
evaluation of potential antipsychotics. Master Thesis in Pharmaceutical
́
(24) Moran-Gates, T.; Massari, C.; Graulich, A.; Liegeois, J.-F.;
Tarazi, F. I. Long-term effects of novel atypical antipsychotic JL13 on
dopamine and serotonin receptor subtypes. J. Neurosci. Res. 2006, 84,
675−682.
(25) Tarazi, F. I.; Moran-Gates, T.; Gardner, M.; Graulich, A.; Lamy,
́
C.; Liegeois, J.-F. Long-term effects of JL13, a potential atypical
antipsychotic, on ionotropic glutamate receptors. J. Mol. Neurosci.
2007, 32, 192−198.
́
(26) Liegeois, J.-F.; Mouithys-Mickalad, A.; Bruhwyler, J.; Delarge, J.;
Petit, C.; Kauffmann, J.-M.; Lamy, M. JL13, a potential successor to
clozapine is less sensitive to oxidative phenomenons. Biochem. Biophys.
Res. Commun. 1997, 238, 252−255.
́
(27) Liegeois, J.-F.; Rogister, F.; Delarge, J.; Pincemail, J. Peroxidase-
catalysed oxidation of different dibenzazepine derivatives. Arch. Pharm.
(Weinheim) 1995, 328, 109−112.
(28) Lieg
Gec
́
eois, J.-F.; Bruhwyler, J.; Petit, C.; Damas, J.; Delarge, J.;
zy, J.; Kauffmann, J.-M.; Lamy, M.; Meltzer, H. Y.; Mouithys-
́
Mickalad, A. Oxidation sensitivity may be a useful tool for the
detection of the hematotoxic potential of newly developed molecules:
Application to antipsychotic drugs. Arch. Biochem. Biophys. 1999, 370,
126−137.
́
(29) Dilly, S.; Liegeois, J.-F. The formation of nitrenium ion also
influences binding of clozapine on rat D2 dopamine receptors:
docking studies and in vitro binding assays. J. Comput.-Aided Mol. Des.
2011, 25, 163−169.
Sciences, University of Liege, 2005
̀
(46) Florijn, W. J.; Tarazi, F. I.; Creese, I. Dopamine receptor
subtypes: Differential regulation after 8 months treatment with
antipsychotic drugs. J. Pharmacol. Exp. Ther. 2007, 280, 561−569.
(47) Tarazi, F. I.; Zhang, K.; Baldessarini, R. J. Long-term effects of
olanzapine, risperidone, and quetiapine on serotonin 1A, 2A and 2C
receptors in rat forebrain regions. Psychopharmacology 2002, 161,
263−270.
́
(30) Liegeois, J.-F.; Rogister, F.; Bruhwyler, J.; Damas, J.; Nguyen, T.
P.; Inarejos, M. O.; Chleide, E.; Mercier, M.; Delarge, J.
Pyridobenzoxazepine and pyridobenzothiazepine derivatives as
potential central nervous system agents: Synthesis and neurochemical
study. J. Med. Chem. 1994, 37, 519−525.
(31) Lieg
́
eois, J.-F.; Bruhwyler, J.; Damas, J.; Nguyen, T. P.; Chleide,
(48) Ho, B. Y.; Karschin, A.; Branchek, T.; Davidson, N.; Lester, H.
A. The role of conserved aspartate and serine residues in ligand
binding and in function of the 5-HT1A receptor: A site-directed
mutation study. Febs Lett. 1992, 312, 259−262.
(49) Strader, C. D.; Candelore, M. R.; Hill, W. S.; Sigal, I. S.; Dixon,
R. A. F. Identification of two serine residues involved in agonist
activation of the beta-adrenergic receptor. J. Biol. Chem. 1989, 264,
13572−13578.
(50) Hibert, M. F.; Trumpp-Kallmeyer, S.; Bruinvels, A.; Hoflack, J.
Three-dimensional models of neurotransmitter G-binding protein-
coupled receptors. Mol. Pharmacol. 1991, 40, 8−15.
(51) Trumpp-Kallmeyer, S.; Hoflack, J.; Bruinvels, A.; Hibert, M. F.
Modeling of G-protein-coupled receptors: application to dopamine,
adrenaline, serotonin, acetylcholine, and mammalian opsin receptors. J.
Med. Chem. 1992, 35, 3448−3462.
(52) Carelli, R. M. The nucleus accumbens and reward: Neuro-
physiological investigations in behaving animals. Behav. Cogn. Neurosci.
Rev. 2002, 1, 281−296.
(53) Tarazi, F. I.; Zhang, K.; Baldessarini, R. J. Long-term effects of
olanzapine, risperidone, and quetiapine on dopamine receptor types in
regions of rat brain: implications for antipsychotic drug treatment. J.
Pharmacol. Exp. Ther. 2001, 297, 711−717.
(54) Simpson, M. D.; Lubman, D. I.; Slater, P.; Deakin, J. F.
Autoradiography with [3H]8-OH-DPAT reveals increases in 5-HT1A
receptors in ventral prefrontal cortex in schizophrenia. Biol. Psychiatry
1996, 39, 919−928.
E.; Mercier, M.; Rogister, F.; Delarge, J. New pyridobenzodiazepine
derivatives as potential antipsychotics: synthesis and neurochemical
study. J. Med. Chem. 1993, 36, 2107−2114.
(32) Lieg
́
eois, J.-F.; Eyrolles, L.; Carato, P.; Bruhwyler, J.; Gec
́
zy, J.;
Damas, J.; Delarge, J. New pyridobenzodiazepine derivatives as
potentially centrally acting drugs. Modifications on the basic side
chain differentially modulate dopamine (D4, D2L) and serotonin (5-
HT2A) binding. J. Med. Chem. 2002, 45, 5136−5149.
(33) Fryer, R. I.; Earley, J. V.; Field, G. F.; Zally, W.; Sternbach, L. H.
A synthesis of amidines from cyclic amides. J. Org. Chem. 1969, 34,
1143−1145.
(34) Goudie, A. J.; Cole, J. C.; Sumnall, H. R. Olanzapine and JL13
induce cross-tolerance to the clozapine discriminative stimulus in rats.
Behav. Pharmacol. 2007, 18, 9−17.
(35) Capuano, B.; Crosby, I. T.; MacRobb, F. M.; Taylor, D. A.;
Vom, A.; Blessing, W. W. JL13 has clozapine-like actions on
thermoregulatory cutaneous blood flow in rats: involvement of
serotonin 5-HT1A and 5-HT2A receptor mechanisms. Prog. Neuro-
psychopharmacol. Biol. Psychiatry 2010, 34, 136−142.
(36) Capuano, B.; Crosby, I. T.; Lloyd, E. J.; Neve, J. E.; Taylor, D. A.
Aminimides as potential CNS acting agents. I. Design, synthesis, and
receptor binding of 4′-aryl aminimide analogues of clozapine as
prospective novel antipsychotics. Aust. J. Chem. 2007, 60, 673−684.
(37) Capuano, B.; Crosby, I. T.; Lloyd, E. J.; Taylor, D. A. Synthesis
and preliminary pharmacological evaluation of 4′-arylalkyl analogues of
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