Targeting the 5-HT2C Receptor in Biological Context and the Current State of 5-HT2C Receptor Ligand Development

Author(s): Eric A. Wold, Christopher T. Wild, Kathryn A. Cunningham, Jia Zhou*

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 16 , 2019

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Graphical Abstract:


Serotonin (5-HT) 5-HT2C receptor (5-HT2CR) is recognized as a critical mediator of diseaserelated pathways and behaviors based upon actions in the central nervous system (CNS). Since 5-HT2CR is a class A G protein-coupled receptor (GPCR), drug discovery efforts have traditionally pursued the activation of the receptor through synthetic ligands with agonists proposed for the treatment of obesity, substance use disorders and impulse control disorders while antagonists may add value for the treatment of anxiety, depression and schizophrenia. The most significant agonist discovery to date is the FDAapproved anti-obesity medication lorcaserin. In recent years, efforts towards developing other mechanisms to enhance receptor function have resulted in the discovery of Positive Allosteric Modulators (PAMs) for the 5-HT2CR, with several molecule series now reported. The biological significance and context for signaling and function of the 5-HT2CR, and the current status of 5-HT2CR agonists and PAMs are discussed in this review.

Keywords: 5-HT2C receptor, Agonists, Allosteric modulation, Positive allosteric modulators, Target selectivity, Signaling bias, Drug discovery, Ligand development, Pharmacological probes, Central nervous system disorders, Neurotherapeutics.

Hauser, A.S.; Attwood, M.M.; Rask-Andersen, M.; Schiöth, H.B.; Gloriam, D.E. Trends in GPCR drug discovery: new agents, targets and indications. Nat. Rev. Drug Discov., 2017, 16(12), 829-842.
[] [PMID: 29075003]
Wild, C.; Cunningham, K.A.; Zhou, J. Allosteric modulation of G protein-coupled receptors: An emerging approach of drug discovery. Austin J. Pharmacol. Ther., 2014, 2(1), 1-8.
[PMID: 27148592]
Hannon, J.; Hoyer, D. Molecular biology of 5-HT receptors. Behav. Brain Res., 2008, 195(1), 198-213.
[] [PMID: 18571247]
Kroeze, W.K.; Roth, B.L. Molecular biology and genomic organization of g protein-coupled serotonin receptors. In: Roth B.L. (eds)The serotonin receptors. The receptors; Humana Press, 2006, pp. 1-38.
Peng, Y.; McCorvy, J.D.; Harpsoe, K.; Lansu, K.; Yuan, S.; Popov, P.; Qu, L.; Pu, M.; Che, T.; Nikolajsen, L.F.; Huang, X.P.; Wu, Y.; Shen, L.; Bjorn-Yoshimoto, W.E.; Ding, K.; Wacker, D.; Han, G.W.; Cheng, J.; Katritch, V.; Jensen, A.A.; Hanson, M.A.; Zhao, S.; Gloriam, D.E.; Roth, B.L.; Stevens, R.C.; Liu, Z.J. 5-HT2C receptor structures reveal the structural basis of GPCR polypharmacology. Cell, 2018, 172(4), 719-730.
Heifetz, A.; Storer, R.I.; McMurray, G.; James, T.; Morao, I.; Aldeghi, M.; Bodkin, M.J.; Biggin, P.C. Application of an integrated GPCR SAR-modeling platform to explain the activation selectivity of human 5-HT2C over 5-HT2B. ACS Chem. Biol., 2016, 11(5), 1372-1382.
[] [PMID: 26900768]
Raymond, J.R.; Mukhin, Y.V.; Gelasco, A.; Turner, J.; Collinsworth, G.; Gettys, T.W.; Grewal, J.S.; Garnovskaya, M.N. Multiplicity of mechanisms of serotonin receptor signal transduction. Pharmacol. Ther., 2001, 92(2-3), 179-212.
[] [PMID: 11916537]
Millan, M.J.; Marin, P.; Bockaert, J.; Mannoury la Cour, C. Signaling at G-protein-coupled serotonin receptors: recent advances and future research directions. Trends Pharmacol. Sci., 2008, 29(9), 454-464.
[] [PMID: 18676031]
Seitz, P.K.; Bremer, N.M.; McGinnis, A.G.; Cunningham, K.A.; Watson, C.S. Quantitative changes in intracellular calcium and extracellular-regulated kinase activation measured in parallel in CHO cells stably expressing serotonin (5-HT) 5-HT2A or 5-HT2C receptors. BMC Neurosci., 2012, 13(25), 25.
[] [PMID: 22397586]
Roth, B.L.; Willins, D.L.; Kristiansen, K.; Kroeze, W.K. 5-Hydroxytryptamine2-family receptors (5-hydroxytryptamine2A, 5-hydroxytryptamine2B, 5-hydroxytryptamine2C): where structure meets function. Pharmacol. Ther., 1998, 79(3), 231-257.
[] [PMID: 9776378]
Burke, J.E.; Dennis, E.A. Phospholipase A2 structure/function, mechanism, and signaling. J. Lipid Res., 2009, 50(Suppl.), S237-S242.
Berg, K.A.; Maayani, S.; Goldfarb, J.; Scaramellini, C.; Leff, P.; Clarke, W.P. Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus. Mol. Pharmacol., 1998, 54(1), 94-104.
[] [PMID: 9658194]
Werry, T.D.; Stewart, G.D.; Crouch, M.F.; Watts, A.; Sexton, P.M.; Christopoulos, A. Pharmacology of 5HT(2C) receptor-mediated ERK1/2 phosphorylation: agonist-specific activation pathways and the impact of RNA editing. Biochem. Pharmacol., 2008, 76(10), 1276-1287.
[] [PMID: 18812172]
Werry, T.D.; Gregory, K.J.; Sexton, P.M.; Christopoulos, A. Characterization of serotonin 5-HT2C receptor signaling to extracellular signal-regulated kinases 1 and 2. J. Neurochem., 2005, 93(6), 1603-1615.
[] [PMID: 15935077]
Lauffer, L.; Glas, E.; Gudermann, T.; Breit, A. Endogenous 5-HT2C receptors phosphorylate the cAMP response element binding protein via protein kinase C-promoted activation of extracellular-regulated kinases-1/2 in hypothalamic mHypoA-2/10 cells. J. Pharmacol. Exp. Ther., 2016, 358(1), 39-49.
[] [PMID: 27189964]
O’Neil, R.T.; Emeson, R.B. Quantitative analysis of 5HT(2C) receptor RNA editing patterns in psychiatric disorders. Neurobiol. Dis., 2012, 45(1), 8-13.
[] [PMID: 21914481]
Marion, S.; Weiner, D.M.; Caron, M.G. RNA editing induces variation in desensitization and trafficking of 5-hydroxytryptamine 2c receptor isoforms. J. Biol. Chem., 2004, 279(4), 2945-2954.
[] [PMID: 14602721]
Werry, T.D.; Loiacono, R.; Sexton, P.M.; Christopoulos, A. RNA editing of the serotonin 5HT2C receptor and its effects on cell signalling, pharmacology and brain function. Pharmacol. Ther., 2008, 119(1), 7-23.
[] [PMID: 18554725]
Schaub, M.; Keller, W. RNA editing by adenosine deaminases generates RNA and protein diversity. Biochimie, 2002, 84(8), 791-803.
[] [PMID: 12457566]
Chen, C.X.; Cho, D.S.; Wang, Q.; Lai, F.; Carter, K.C.; Nishikura, K. A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains. RNA, 2000, 6(5), 755-767.
[] [PMID: 10836796]
Valente, L.; Nishikura, K. ADAR gene family and A-to-I RNA editing: Diverse roles in posttranscriptional gene regulation. In: Progress in Nucleic Acid Research and Molecular Biology; Academic Press, 2005, Vol. 79, pp. 299-338.
Herrick-Davis, K.; Grinde, E.; Niswender, C.M. Serotonin 5-HT2C receptor RNA editing alters receptor basal activity: implications for serotonergic signal transduction. J. Neurochem., 1999, 73(4), 1711-1717.
[] [PMID: 10501219]
Berg, K.A.; Cropper, J.D.; Niswender, C.M.; Sanders-Bush, E.; Emeson, R.B.; Clarke, W.P. RNA-editing of the 5-HT(2C) receptor alters agonist-receptor-effector coupling specificity. Br. J. Pharmacol., 2001, 134(2), 386-392.
[] [PMID: 11564657]
Maydanovych, O.; Beal, P.A. Breaking the central dogma by RNA editing. Chem. Rev., 2006, 106(8), 3397-3411.
[] [PMID: 16895334]
Herrick-Davis, K.; Grinde, E.; Lindsley, T.; Teitler, M.; Mancia, F.; Cowan, A.; Mazurkiewicz, J.E. Native serotonin 5-HT2C receptors are expressed as homodimers on the apical surface of choroid plexus epithelial cells. Mol. Pharmacol., 2015, 87(4), 660-673.
[] [PMID: 25609374]
Herrick-Davis, K.F.; Dinah, T. 5-HT2C receptors in the pathophysiology of CNS disease. British Journal of Clinical Pharmacology: Blackwell Science Inc, 2011, 72, 129-155.
Schellekens, H.; van Oeffelen, W.E.; Dinan, T.G.; Cryan, J.F. Promiscuous dimerization of the growth hormone secretagogue receptor (GHS-R1a) attenuates ghrelin-mediated signaling. J. Biol. Chem., 2013, 288(1), 181-191.
[] [PMID: 23161547]
Felsing, D.E.; Anastasio, N.C.; Miszkiel, J.M.; Gilbertson, S.R.; Allen, J.A.; Cunningham, K.A. Biophysical validation of serotonin 5-HT2A and 5-HT2C receptor interaction. PLoS One, 2018, 13(8), e0203137.
[] [PMID: 30157263]
Price, A.E.; Sholler, D.J.; Stutz, S.J.; Anastasio, N.C.; Cunningham, K.A. Endogenous serotonin 5-HT2A and 5-HT2C receptors associate in the medial prefrontal cortex. ACS Chem. Neurosci., 2019, 21(5), 1532-1537.
[] [PMID: 30645940]
Kamal, M.; Gbahou, F.; Guillaume, J.L.; Daulat, A.M.; Benleulmi-Chaachoua, A.; Luka, M.; Chen, P.; Kalbasi Anaraki, D.; Baroncini, M.; Mannoury la Cour, C.; Millan, M.J.; Prevot, V.; Delagrange, P.; Jockers, R. Convergence of melatonin and serotonin (5-HT) signaling at MT2/5-HT2C receptor heteromers. J. Biol. Chem., 2015, 290(18), 11537-11546.
[] [PMID: 25770211]
Moutkine, I.; Quentin, E.; Guiard, B.P.; Maroteaux, L.; Doly, S. Heterodimers of serotonin receptor subtypes 2 are driven by 5-HT2C protomers. J. Biol. Chem., 2017, 292(15), 6352-6368.
[] [PMID: 28258217]
Bigford, G.E.; Chaudhry, N.S.; Keane, R.W.; Holohean, A.M. 5-Hydroxytryptamine 5HT2C receptors form a protein complex with N-methyl-D-aspartate GluN2A subunits and activate phosphorylation of Src protein to modulate motoneuronal depolarization. J. Biol. Chem., 2012, 287(14), 11049-11059.
[] [PMID: 22291020]
Anastasio, N.C.; Gilbertson, S.R.; Bubar, M.J.; Agarkov, A.; Stutz, S.J.; Jeng, Y.; Bremer, N.M.; Smith, T.D.; Fox, R.G.; Swinford, S.E.; Seitz, P.K.; Charendoff, M.N.; Craft, J.W., Jr; Laezza, F.M.; Watson, C.S.; Briggs, J.M.; Cunningham, K.A. Peptide inhibitors disrupt the serotonin 5-HT2C receptor interaction with phosphatase and tensin homolog to allosterically modulate cellular signaling and behavior. J. Neurosci., 2013, 33(4), 1615-1630.
[] [PMID: 23345234]
Bohn, L.M.; Schmid, C.L. Serotonin receptor signaling and regulation via β-arrestins. Crit. Rev. Biochem. Mol. Biol., 2010, 45(6), 555-566.
[] [PMID: 20925600]
Howell, L.L.; Cunningham, K.A. Serotonin 5-HT2 receptor interactions with dopamine function: implications for therapeutics in cocaine use disorder. Pharmacol. Rev., 2015, 67(1), 176-197.
[] [PMID: 25505168]
Anastasio, N.C.; Stutz, S.J.; Fink, L.H.; Swinford-Jackson, S.E.; Sears, R.M.; DiLeone, R.J.; Rice, K.C.; Moeller, F.G.; Cunningham, K.A. Serotonin (5-HT) 5-HT2A receptor (5-HT2AR):5-HT2CR imbalance in medial prefrontal cortex associates with motor impulsivity. ACS Chem. Neurosci., 2015, 6(7), 1248-1258.
[] [PMID: 26120876]
Prisco, S.; Pagannone, S.; Esposito, E. Serotonin-dopamine interaction in the rat ventral tegmental area: an electrophysiological study in vivo. J. Pharmacol. Exp. Ther., 1994, 271(1), 83-90.
[PMID: 7965760]
Di Giovanni, G.; Di Matteo, V.; La Grutta, V.; Esposito, E. m-Chlorophenylpiperazine excites non-dopaminergic neurons in the rat substantia nigra and ventral tegmental area by activating serotonin-2C receptors. Neuroscience, 2001, 103(1), 111-116.
[] [PMID: 11311791]
Theile, J.W.; Morikawa, H.; Gonzales, R.A.; Morrisett, R.A. Role of 5-hydroxytryptamine2C receptors in Ca2+-dependent ethanol potentiation of GABA release onto ventral tegmental area dopamine neurons. J. Pharmacol. Exp. Ther., 2009, 329(2), 625-633.
[] [PMID: 19225162]
Kasper, J.M.; Booth, R.G.; Peris, J. Serotonin-2C receptor agonists decrease potassium-stimulated GABA release in the nucleus accumbens. Synapse, 2015, 69(2), 78-85.
[] [PMID: 25382408]
Di Giovanni, G.; De Deurwaerdére, P.; Di Mascio, M.; Di Matteo, V.; Esposito, E.; Spampinato, U. Selective blockade of serotonin-2C/2B receptors enhances mesolimbic and mesostriatal dopaminergic function: a combined in vivo electrophysiological and microdialysis study. Neuroscience, 1999, 91(2), 587-597.
[] [PMID: 10366016]
Gobert, A.; Rivet, J-M.; Lejeune, F.; Newman-Tancredi, A.; Adhumeau-Auclair, A.; Nicolas, J-P.; Cistarelli, L.; Melon, C.; Millan, M.J. Serotonin(2C) receptors tonically suppress the activity of mesocortical dopaminergic and adrenergic, but not serotonergic, pathways: a combined dialysis and electrophysiological analysis in the rat. Synapse, 2000, 36(3), 205-221.
[<205:AID-SYN5>3.0.CO;2-D] [PMID: 10819900]
Bubar, M.J.; Stutz, S.J.; Cunningham, K.A. 5-HT(2C) receptors localize to dopamine and GABA neurons in the rat mesoaccumbens pathway. PLoS One, 2011, 6(6), e20508.
[] [PMID: 21687728]
Bubar, M.J.; Cunningham, K.A. Distribution of serotonin 5-HT2C receptors in the ventral tegmental area. Neuroscience, 2007, 146(1), 286-297.
[] [PMID: 17367945]
Xu, P.; He, Y.; Cao, X.; Valencia-Torres, L.; Yan, X.; Saito, K.; Wang, C.; Yang, Y.; Hinton, A., Jr; Zhu, L.; Shu, G.; Myers, M.G., Jr; Wu, Q.; Tong, Q.; Heisler, L.K.; Xu, Y. Activation of serotonin 2C receptors in dopamine neurons inhibits binge-like eating in mice. Biol. Psychiatry, 2017, 81(9), 737-747.
[] [PMID: 27516377]
Santana, N.; Artigas, F. Expression of serotonin2C receptors in pyramidal and GABAergic neurons of rat prefrontal cortex: a comparison with striatum. Cereb. Cortex, 2017, 27(6), 3125-3139.
[PMID: 27252352]
Liu, S.; Bubar, M.J.; Lanfranco, M.F.; Hillman, G.R.; Cunningham, K.A. Serotonin2C receptor localization in GABA neurons of the rat medial prefrontal cortex: implications for understanding the neurobiology of addiction. Neuroscience, 2007, 146(4), 1677-1688.
[] [PMID: 17467185]
Anastasio, N.C.; Stutz, S.J.; Fox, R.G.; Sears, R.M.; Emeson, R.B.; DiLeone, R.J.; O’Neil, R.T.; Fink, L.H.; Li, D.; Green, T.A.; Moeller, F.G.; Cunningham, K.A. Functional status of the serotonin 5-HT2C receptor (5-HT2CR) drives interlocked phenotypes that precipitate relapse-like behaviors in cocaine dependence. Neuropsychopharmacology, 2014, 39(2), 370-382.
[] [PMID: 23939424]
Bubar, M.J.; Cunningham, K.A. Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence. Curr. Top. Med. Chem., 2006, 6(18), 1971-1985.
[] [PMID: 17017968]
Cunningham, K.A.; Anastasio, N.C.; Fox, R.G.; Stutz, S.J.; Bubar, M.J.; Swinford, S.E.; Watson, C.S.; Gilbertson, S.R.; Rice, K.C.; Rosenzweig-Lipson, S.; Moeller, F.G. Synergism between a serotonin 5-HT2A receptor (5-HT2AR) antagonist and 5-HT2CR agonist suggests new pharmacotherapeutics for cocaine addiction. ACS Chem. Neurosci., 2013, 4(1), 110-121.
[] [PMID: 23336050]
Thomsen, W.J.; Grottick, A.J.; Menzaghi, F.; Reyes-Saldana, H.; Espitia, S.; Yuskin, D.; Whelan, K.; Martin, M.; Morgan, M.; Chen, W.; Al-Shamma, H.; Smith, B.; Chalmers, D.; Behan, D. Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J. Pharmacol. Exp. Ther., 2008, 325(2), 577-587.
[] [PMID: 18252809]
Hoy, S.M. Lorcaserin: A review of its use in chronic weight management. Drugs, 2013, 73(5), 463-473.
[] [PMID: 23529825]
Harvey-Lewis, C.; Li, Z.; Higgins, G.A.; Fletcher, P.J. The 5-HT(2C) receptor agonist lorcaserin reduces cocaine self-administration, reinstatement of cocaine-seeking and cocaine induced locomotor activity. Neuropharmacology, 2016, 101, 237-245.
[] [PMID: 26427596]
Di Giovanni, G.; De Deurwaerdère, P. New therapeutic opportunities for 5-HT2C receptor ligands in neuropsychiatric disorders. Pharmacol. Ther., 2016, 157, 125-162.
[] [PMID: 26617215]
Higgins, G.A.; Fletcher, P.J. Therapeutic potential of 5-HT2C receptor agonists for addictive disorders. ACS Chem. Neurosci., 2015, 6(7), 1071-1088.
[] [PMID: 25870913]
Tecott, L.H.; Sun, L.M.; Akana, S.F.; Strack, A.M.; Lowenstein, D.H.; Dallman, M.F.; Julius, D. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature, 1995, 374(6522), 542-546.
[] [PMID: 7700379]
Nonogaki, K.; Ohba, Y.; Sumii, M.; Oka, Y. Serotonin systems upregulate the expression of hypothalamic NUCB2 via 5-HT2C receptors and induce anorexia via a leptin-independent pathway in mice. Biochem. Biophys. Res. Commun., 2008, 372(1), 186-190.
[] [PMID: 18477467]
Wirshing, D.A.; Wirshing, W.C.; Kysar, L.; Berisford, M.A.; Goldstein, D.; Pashdag, J.; Mintz, J.; Marder, S.R. Novel antipsychotics: comparison of weight gain liabilities. J. Clin. Psychiatry, 1999, 60(6), 358-363.
[] [PMID: 10401912]
Kirk, S.L.; Glazebrook, J.; Grayson, B.; Neill, J.C.; Reynolds, G.P. Olanzapine-induced weight gain in the rat: role of 5-HT2C and histamine H1 receptors. Psychopharmacology (Berl.), 2009, 207(1), 119-125.
[] [PMID: 19688201]
Ge, T.; Zhang, Z.; Lv, J.; Song, Y.; Fan, J.; Liu, W.; Wang, X.; Hall, F.S.; Li, B.; Cui, R. The role of 5-HT2c receptor on corticosterone-mediated food intake. J. Biochem. Mol. Toxicol., 2017, 31(6)
[] [PMID: 28186389]
Halford, J.C.; Lawton, C.L.; Blundell, J.E. The 5-HT2 receptor agonist MK-212 reduces food intake and increases resting but prevents the behavioural satiety sequence. Pharmacol. Biochem. Behav., 1997, 56(1), 41-46.
[] [PMID: 8981607]
Wacker, D.A.; Miller, K.J. Agonists of the serotonin 5-HT2C receptor: preclinical and clinical progression in multiple diseases. Curr. Opin. Drug Discov. Devel., 2008, 11(4), 438-445.
[PMID: 18600561]
Dunlop, J.; Sabb, A.L.; Mazandarani, H.; Zhang, J.; Kalgaonker, S.; Shukhina, E.; Sukoff, S.; Vogel, R.L.; Stack, G.; Schechter, L.; Harrison, B.L.; Rosenzweig-Lipson, S. WAY-163909 [(7bR, 10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole], a novel 5-hydroxytryptamine 2C receptor-selective agonist with anorectic activity. J. Pharmacol. Exp. Ther., 2005, 313(2), 862-869.
[] [PMID: 15705738]
Voigt, J.P.; Fink, H. Serotonin controlling feeding and satiety. Behav. Brain Res., 2015, 277, 14-31.
[] [PMID: 25217810]
Gautron, L.; Elmquist, J.K.; Williams, K.W. Neural control of energy balance: Translating circuits to therapies. Cell, 2015, 161(1), 133-145.
[] [PMID: 25815991]
Smith, S.R.; Prosser, W.A.; Donahue, D.J.; Morgan, M.E.; Anderson, C.M.; Shanahan, W.R.; Group, A.P.D.S. Lorcaserin (APD356), a selective 5-HT(2C) agonist, reduces body weight in obese men and women. Obesity (Silver Spring), 2009, 17(3), 494-503.
[] [PMID: 19057523]
Bubar, M.J.; Cunningham, K.A. Prospects for serotonin 5-HT2R pharmacotherapy in psychostimulant abuse. Prog. Brain Res; , 2008, 172, pp. 319-346.
[] [PMID: 18772040]
Neelakantan, H.; Holliday, E.D.; Fox, R.G.; Stutz, S.J.; Comer, S.D.; Haney, M.; Anastasio, N.C.; Moeller, F.G.; Cunningham, K.A. Lorcaserin suppresses oxycodone self-administration and relapse vulnerability in rats. ACS Chem. Neurosci., 2017, 8(5), 1065-1073.
[] [PMID: 28107783]
Moeller, F.G.; Cunningham, K.A. Innovative therapeutic intervention for opioid use disorder. Neuropsychopharmacology, 2018, 43(1), 220-221.
[] [PMID: 29192668]
Swinford-Jackson, S.E.; Anastasio, N.C.; Fox, R.G.; Stutz, S.J.; Cunningham, K.A. Incubation of cocaine cue reactivity associates with neuroadaptations in the cortical serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system. Neuroscience, 2016, 324, 50-61.
[] [PMID: 26926963]
Cunningham, K.A.; Fox, R.G.; Anastasio, N.C.; Bubar, M.J.; Stutz, S.J.; Moeller, F.G.; Gilbertson, S.R.; Rosenzweig-Lipson, S. Selective serotonin 5-HT(2C) receptor activation suppresses the reinforcing efficacy of cocaine and sucrose but differentially affects the incentive-salience value of cocaine- vs. sucrose-associated cues. Neuropharmacology, 2011, 61(3), 513-523.
[] [PMID: 21575646]
Grottick, A.J.; Fletcher, P.J.; Higgins, G.A. Studies to investigate the role of 5-HT(2C) receptors on cocaine- and food-maintained behavior. J. Pharmacol. Exp. Ther., 2000, 295(3), 1183-1191.
[PMID: 11082456]
Manvich, D.F.; Kimmel, H.L.; Cooper, D.A.; Howell, L.L. The serotonin 2C receptor antagonist SB 242084 exhibits abuse-related effects typical of stimulants in squirrel monkeys. J. Pharmacol. Exp. Ther., 2012, 342(3), 761-769.
[] [PMID: 22685342]
Manvich, D.F.; Kimmel, H.L.; Howell, L.L. Effects of serotonin 2C receptor agonists on the behavioral and neurochemical effects of cocaine in squirrel monkeys. J. Pharmacol. Exp. Ther., 2012, 341(2), 424-434.
[] [PMID: 22328576]
Pelloux, Y.; Dilleen, R.; Economidou, D.; Theobald, D.; Everitt, B.J. Reduced forebrain serotonin transmission is causally involved in the development of compulsive cocaine seeking in rats. Neuropsychopharmacology, 2012, 37(11), 2505-2514.
[] [PMID: 22763621]
Fletcher, P.J.; Grottick, A.J.; Higgins, G.A. Differential effects of the 5-HT(2A) receptor antagonist M100907 and the 5-HT(2C) receptor antagonist SB242084 on cocaine-induced locomotor activity, cocaine self-administration and cocaine-induced reinstatement of responding. Neuropsychopharmacology, 2002, 27(4), 576-586.
[PMID: 12377394]
Shanahan, W.R.; Rose, J.E.; Glicklich, A.; Stubbe, S.; Sanchez-Kam, M. Lorcaserin for smoking cessation and associated weight gain: a randomized 12-week clinical trial. Nicotine Tob. Res., 2017, 19(8), 944-951.
[PMID: 27815511]
Farr, O.M.; Upadhyay, J.; Gavrieli, A.; Camp, M.; Spyrou, N.; Kaye, H.; Mathew, H.; Vamvini, M.; Koniaris, A.; Kilim, H.; Srnka, A.; Migdal, A.; Mantzoros, C.S. Lorcaserin administration decreases activation of brain centers in response to food cues and these emotion- and salience-related changes correlate with weight loss effects: a 4-week-long randomized, placebo-controlled, double-blind clinical trial. Diabetes, 2016, 65(10), 2943-2953.
[] [PMID: 27385157]
Cunningham, K.A.; Anastasio, N.C. Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction. Neuropharmacology,, 2014, 76(Pt B). , 460-478.
Moeller, F.G.; Barratt, E.S.; Dougherty, D.M.; Schmitz, J.M.; Swann, A.C. Psychiatric aspects of impulsivity. Am. J. Psychiatry, 2001, 158(11), 1783-1793.
[] [PMID: 11691682]
Liu, S.; Lane, S.D.; Schmitz, J.M.; Waters, A.J.; Cunningham, K.A.; Moeller, F.G. Relationship between attentional bias to cocaine-related stimuli and impulsivity in cocaine-dependent subjects. Am. J. Drug Alcohol Abuse, 2011, 37(2), 117-122.
[] [PMID: 21204739]
Leung, D.; Staiger, P.K.; Hayden, M.; Lum, J.A.; Hall, K.; Manning, V.; Verdejo-Garcia, A. Meta-analysis of the relationship between impulsivity and substance-related cognitive biases. Drug Alcohol Depend., 2017, 172, 21-33.
[] [PMID: 28107679]
Fletcher, P.J.; Tampakeras, M.; Sinyard, J.; Higgins, G.A. Opposing effects of 5-HT(2A) and 5-HT(2C) receptor antagonists in the rat and mouse on premature responding in the five-choice serial reaction time test. Psychopharmacology (Berl.), 2007, 195(2), 223-234.
[] [PMID: 17673981]
Winstanley, C.A.; Theobald, D.E.; Dalley, J.W.; Glennon, J.C.; Robbins, T.W. 5-HT2A and 5-HT2C receptor antagonists have opposing effects on a measure of impulsivity: interactions with global 5-HT depletion. Psychopharmacology (Berl.), 2004, 176(3-4), 376-385.
[] [PMID: 15232674]
Pennanen, L.; van der Hart, M.; Yu, L.; Tecott, L.H. Impact of serotonin (5-HT)2C receptors on executive control processes. Neuropsychopharmacology, 2013, 38(6), 957-967.
[] [PMID: 23303047]
Besson, M.; Pelloux, Y.; Dilleen, R.; Theobald, D.E.; Lyon, A.; Belin-Rauscent, A.; Robbins, T.W.; Dalley, J.W.; Everitt, B.J.; Belin, D. Cocaine modulation of frontostriatal expression of Zif268, D2, and 5-HT2c receptors in high and low impulsive rats. Neuropsychopharmacology, 2013, 38(10), 1963-1973.
[] [PMID: 23632436]
Anastasio, N.C.; Liu, S.; Maili, L.; Swinford, S.E.; Lane, S.D.; Fox, R.G.; Hamon, S.C.; Nielsen, D.A.; Cunningham, K.A.; Moeller, F.G. Variation within the serotonin (5-HT) 5-HT2C receptor system aligns with vulnerability to cocaine cue reactivity. Transl. Psychiatry, 2014, 4, e369.
[] [PMID: 24618688]
Everitt, B.J.; Robbins, T.W. Drug addiction: updating actions to habits to compulsions ten years on. Annu. Rev. Psychol., 2016, 67, 23-50.
[] [PMID: 26253543]
Nichols, D.E. Hallucinogens. Pharmacol. Ther., 2004, 101(2), 131-181.
[] [PMID: 14761703]
Fitzgerald, L.W.; Burn, T.C.; Brown, B.S.; Patterson, J.P.; Corjay, M.H.; Valentine, P.A.; Sun, J.H.; Link, J.R.; Abbaszade, I.; Hollis, J.M.; Largent, B.L.; Hartig, P.R.; Hollis, G.F.; Meunier, P.C.; Robichaud, A.J.; Robertson, D.W. Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine. Mol. Pharmacol., 2000, 57(1), 75-81.
[PMID: 10617681]
Connolly, H.M.; Crary, J.L.; McGoon, M.D.; Hensrud, D.D.; Edwards, B.S.; Edwards, W.D.; Schaff, H.V. Valvular heart disease associated with fenfluramine-phentermine. N. Engl. J. Med., 1997, 337(9), 581-588.
[] [PMID: 9271479]
Shram, M.J.; Schoedel, K.A.; Bartlett, C.; Shazer, R.L.; Anderson, C.M.; Sellers, E.M. Evaluation of the abuse potential of lorcaserin, a serotonin 2C (5-HT2C) receptor agonist, in recreational polydrug users. Clin. Pharmacol. Ther., 2011, 89(5), 683-692.
[] [PMID: 21412231]
Greenway, F.L.; Shanahan, W.; Fain, R.; Ma, T.; Rubino, D. Safety and tolerability review of lorcaserin in clinical trials. Clin. Obes., 2016, 6(5), 285-295.
[] [PMID: 27627785]
Kalgutkar, A.S.; Dalvie, D.K.; Aubrecht, J.; Smith, E.B.; Coffing, S.L.; Cheung, J.R.; Vage, C.; Lame, M.E.; Chiang, P.; McClure, K.F.; Maurer, T.S.; Coelho, R.V., Jr; Soliman, V.F.; Schildknegt, K. Genotoxicity of 2-(3-chlorobenzyloxy)-6-(piperazinyl)pyrazine, a novel 5-hydroxytryptamine2c receptor agonist for the treatment of obesity: role of metabolic activation. Drug Metab. Dispos., 2007, 35(6), 848-858.
[] [PMID: 17344339]
Kelly, C.R.; Sharif, N.A. Pharmacological evidence for a functional serotonin-2B receptor in a human uterine smooth muscle cell line. J. Pharmacol. Exp. Ther., 2006, 317(3), 1254-1261.
[] [PMID: 16517693]
Bös, M.; Jenck, F.; Martin, J.R.; Moreau, J.L.; Sleight, A.J.; Wichmann, J.; Widmer, U. Novel agonists of 5HT2C receptors. Synthesis and biological evaluation of substituted 2-(indol-1-yl)-1-methylethylamines and 2-(indeno[1,2-b]pyrrol-1-yl)-1-methyleth-ylamines. Improved therapeutics for obsessive compulsive disorder. J. Med. Chem., 1997, 40(17), 2762-2769.
[] [PMID: 9276022]
Kimura, Y.; Hatanaka, K.; Naitou, Y.; Maeno, K.; Shimada, I.; Koakutsu, A.; Wanibuchi, F.; Yamaguchi, T. Pharmacological profile of YM348, a novel, potent and orally active 5-HT2C receptor agonist. Eur. J. Pharmacol., 2004, 483(1), 37-43.
[] [PMID: 14709324]
Fitzgerald, L.W.; Burn, T.C.; Brown, B.S.; Patterson, J.P.; Corjay, M.H.; Valentine, P.A.; Sun, J-H.; Link, J.R.; Abbaszade, I.; Hollis, J.M.; Largent, B.L.; Hartig, P.R.; Hollis, G.F.; Meunier, P.C.; Robichaud, A.J.; Robertson, D.W. Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine. Mol. Pharmacol., 2000, 57(1), 75-81.
[PMID: 10617681]
Cheng, J.; Giguère, P.M.; Onajole, O.K.; Lv, W.; Gaisin, A.; Gunosewoyo, H.; Schmerberg, C.M.; Pogorelov, V.M.; Rodriguiz, R.M.; Vistoli, G.; Wetsel, W.C.; Roth, B.L.; Kozikowski, A.P. Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents. J. Med. Chem., 2015, 58(4), 1992-2002.
[] [PMID: 25633969]
Cheng, J.; Giguere, P.M.; Schmerberg, C.M.; Pogorelov, V.M.; Rodriguiz, R.M.; Huang, X.P.; Zhu, H.; McCorvy, J.D.; Wetsel, W.C.; Roth, B.L.; Kozikowski, A.P. Further advances in optimizing (2-phenylcyclopropyl)methylamines as novel serotonin 2C agonists: effects on hyperlocomotion, prepulse inhibition, and cognition models. J. Med. Chem., 2016, 59(2), 578-591.
[] [PMID: 26704965]
Zhang, G.; Cheng, J.; McCorvy, J.D.; Lorello, P.J.; Caldarone, B.J.; Roth, B.L.; Kozikowski, A.P. Discovery of N-substituted (2-phenylcyclopropyl)methylamines as functionally selective serotonin 2C receptor agonists for potential use as antipsychotic medications. J. Med. Chem., 2017, 60(14), 6273-6288.
[] [PMID: 28657744]
Siuciak, J.A.; Chapin, D.S.; McCarthy, S.A.; Guanowsky, V.; Brown, J.; Chiang, P.; Marala, R.; Patterson, T.; Seymour, P.A.; Swick, A.; Iredale, P.A. CP-809,101, a selective 5-HT2C agonist, shows activity in animal models of antipsychotic activity. Neuropharmacology, 2007, 52(2), 279-290.
[] [PMID: 16949622]
Fevig, J.M.; Feng, J.; Rossi, K.A.; Miller, K.J.; Wu, G.; Hung, C.P.; Ung, T.; Malmstrom, S.E.; Zhang, G.; Keim, W.J.; Cullen, M.J.; Rohrbach, K.W.; Qu, Q.; Gan, J.; Pelleymounter, M.A.; Robl, J.A. Synthesis and SAR of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones as 5-HT2C receptor agonists. Bioorg. Med. Chem. Lett., 2013, 23(1), 330-335.
[] [PMID: 23177783]
Zhao, G.; Kwon, C.; Bisaha, S.N.; Stein, P.D.; Rossi, K.A.; Cao, X.; Ung, T.; Wu, G.; Hung, C.P.; Malmstrom, S.E.; Zhang, G.; Qu, Q.; Gan, J.; Keim, W.J.; Cullen, M.J.; Rohrbach, K.W.; Devenny, J.; Pelleymounter, M.A.; Miller, K.J.; Robl, J.A. Synthesis and SAR of potent and selective tetrahydropyrazinoisoquinolinone 5-HT(2C) receptor agonists. Bioorg. Med. Chem. Lett., 2013, 23(13), 3914-3919.
[] [PMID: 23683593]
Dunlop, J.; Watts, S.W.; Barrett, J.E.; Coupet, J.; Harrison, B.; Mazandarani, H.; Nawoschik, S.; Pangalos, M.N.; Ramamoorthy, S.; Schechter, L.; Smith, D.; Stack, G.; Zhang, J.; Zhang, G.; Rosenzweig-Lipson, S. Characterization of vabicaserin (SCA-136), a selective 5-hydroxytryptamine 2C receptor agonist. J. Pharmacol. Exp. Ther., 2011, 337(3), 673-680.
[] [PMID: 21402690]
Rouquet, G.; Moore, D.E.; Spain, M.; Allwood, D.M.; Battilocchio, C.; Blakemore, D.C.; Fish, P.V.; Jenkinson, S.; Jessiman, A.S.; Ley, S.V.; McMurray, G.; Storer, R.I. Design, synthesis, and evaluation of tetrasubstituted pyridines as potent 5-HT2C receptor agonists. ACS Med. Chem. Lett., 2015, 6(3), 329-333.
[] [PMID: 25815155]
Storer, R.I.; Brennan, P.E.; Brown, A.D.; Bungay, P.J.; Conlon, K.M.; Corbett, M.S.; DePianta, R.P.; Fish, P.V.; Heifetz, A.; Ho, D.K.; Jessiman, A.S.; McMurray, G.; de Oliveira, C.A.; Roberts, L.R.; Root, J.A.; Shanmugasundaram, V.; Shapiro, M.J.; Skerten, M.; Westbrook, D.; Wheeler, S.; Whitlock, G.A.; Wright, J. Multiparameter optimization in CNS drug discovery: design of pyrimido[4,5-d]azepines as potent 5-hydroxytryptamine 2C (5-HT2C) receptor agonists with exquisite functional selectivity over 5-HT2A and 5-HT2B receptors. J. Med. Chem., 2014, 57(12), 5258-5269.
[] [PMID: 24878222]
Tye, H.; Mueller, S.G.; Prestle, J.; Scheuerer, S.; Schindler, M.; Nosse, B.; Prevost, N.; Brown, C.J.; Heifetz, A.; Moeller, C.; Pedret-Dunn, A.; Whittaker, M. Novel 6,7,8,9-tetrahydro-5H-1,4,7,10a-tetraaza-cyclohepta[f]indene analogues as potent and selective 5-HT(2C) agonists for the treatment of metabolic disorders. Bioorg. Med. Chem. Lett., 2011, 21(1), 34-37.
[] [PMID: 21146986]
Carpenter, J.; Wang, Y.; Wu, G.; Feng, J.; Ye, X.Y.; Morales, C.L.; Broekema, M.; Rossi, K.A.; Miller, K.J.; Murphy, B.J.; Wu, G.; Malmstrom, S.E.; Azzara, A.V.; Sher, P.M.; Fevig, J.M.; Alt, A.; Bertekap, R.L., Jr; Cullen, M.J.; Harper, T.M.; Foster, K.; Luk, E.; Xiang, Q.; Grubb, M.F.; Robl, J.A.; Wacker, D.A. Utilization of an active site mutant receptor for the identification of potent and selective atypical 5-HT2C receptor agonists. J. Med. Chem., 2017, 60(14), 6166-6190.
[] [PMID: 28635286]
Felsing, D.E.; Canal, C.E.; Booth, R.G. Ligand-directed serotonin 5-HT2C receptor desensitization and sensitization. Eur. J. Pharmacol., 2019, 848, 131-139.
[] [PMID: 30689993]
Menniti, F.S.; Lindsley, C.W.; Conn, P.J.; Pandit, J.; Zagouras, P.; Volkmann, R.A. Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks. Curr. Top. Med. Chem., 2013, 13(1), 26-54.
[] [PMID: 23409764]
Christopoulos, A. Allosteric binding sites on cell-surface receptors: novel targets for drug discovery. Nat. Rev. Drug Discov., 2002, 1(3), 198-210.
[] [PMID: 12120504]
Conn, P.J.; Christopoulos, A.; Lindsley, C.W. Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat. Rev. Drug Discov., 2009, 8(1), 41-54.
[] [PMID: 19116626]
Gregory, K.J.; Sexton, P.M.; Christopoulos, A. Overview of receptor allosterism. Curr Protoc Pharmacol, 2010.1, 1.21.1-1.21.34.
Melancon, B.J.; Hopkins, C.R.; Wood, M.R.; Emmitte, K.A.; Niswender, C.M.; Christopoulos, A.; Conn, P.J.; Lindsley, C.W. Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery. J. Med. Chem., 2012, 55(4), 1445-1464.
[] [PMID: 22148748]
Wootten, D.; Christopoulos, A.; Sexton, P.M. Emerging paradigms in GPCR allostery: implications for drug discovery. Nat. Rev. Drug Discov., 2013, 12(8), 630-644.
[] [PMID: 23903222]
Schlag, B.D.; Lou, Z.; Fennell, M.; Dunlop, J. Ligand dependency of 5-hydroxytryptamine 2C receptor internalization. J. Pharmacol. Exp. Ther., 2004, 310(3), 865-870.
[] [PMID: 15113845]
Foster, D.J.; Conn, P.J. Allosteric modulation of GPCRs: new insights and potential utility for treatment of schizophrenia and other CNS disorders. Neuron, 2017, 94(3), 431-446.
[] [PMID: 28472649]
Kenakin, T.P. '7TM receptor allostery: putting numbers to shapeshifting proteins. Trends Pharmacol. Sci., 2009, 30(9), 460-469.
[] [PMID: 19729207]
Christopoulos, A. Advances in G protein-coupled receptor allostery: from function to structure. Mol. Pharmacol., 2014, 86(5), 463-478.
[] [PMID: 25061106]
Wild, C.T.; Miszkiel, J.M.; Wold, E.A.; Soto, C.A.; Ding, C.; Hartley, R.M.; White, M.A.; Anastasio, N.C.; Cunningham, K.A.; Zhou, J. Design, synthesis, and characterization of 4-undecylpipe-ridine-2-carboxamides as positive allosteric modulators of the serotonin (5-HT) 5-HT2C receptor. J. Med. Chem., 2019, 62(1), 288-305.
[] [PMID: 29620897]
Zhou, J.; Cunningham, K.A. Positive-allosteric modulation of the 5-HT2C receptor: implications for neuropsychopharmacology and neurotherapeutics. Neuropsychopharmacology, 2019, 44(1), 230-231.
[] [PMID: 30202047]
Wold, E.A.; Zhou, J. GPCR allosteric modulators: mechanistic advantages and therapeutic applications. Curr. Top. Med. Chem., 2018, 18(23), 2002-2006.
[] [PMID: 30621563]
Dror, R.O.; Green, H.F.; Valant, C.; Borhani, D.W.; Valcourt, J.R.; Pan, A.C.; Arlow, D.H.; Canals, M.; Lane, J.R.; Rahmani, R.; Baell, J.B.; Sexton, P.M.; Christopoulos, A.; Shaw, D.E. Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs. Nature, 2013, 503(7475), 295-299.
[] [PMID: 24121438]
Bridges, T.M.; Lindsley, C.W. G-protein-coupled receptors: from classical modes of modulation to allosteric mechanisms. ACS Chem. Biol., 2008, 3(9), 530-541.
[] [PMID: 18652471]
Lindsley, C.W.; Emmitte, K.A.; Hopkins, C.R.; Bridges, T.M.; Gregory, K.J.; Niswender, C.M.; Conn, P.J. Practical strategies and concepts in GPCR allosteric modulator discovery: recent advances with metabotropic glutamate receptors. Chem. Rev., 2016, 116(11), 6707-6741.
[] [PMID: 26882314]
Merkler, D.J.; Merkler, K.A.; Stern, W.; Fleming, F.F. Fatty acid amide biosynthesis: a possible new role for peptidylglycine alpha-amidating enzyme and acyl-coenzyme A: glycine N-acyltransferase. Arch. Biochem. Biophys., 1996, 330(2), 430-434.
[] [PMID: 8660675]
Conn, P.J.; Lindsley, C.W.; Meiler, J.; Niswender, C.M. Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders. Nat. Rev. Drug Discov., 2014, 13(9), 692-708.
[] [PMID: 25176435]
Wold, E.A.; Chen, J.; Cunningham, K.A.; Zhou, J. Allosteric modulation of class A GPCRs: targets, agents, and emerging concepts. J. Med. Chem., 2019, 62(1), 88-127.
[] [PMID: 30106578]
Im, W.B.; Chio, C.L.; Alberts, G.L.; Dinh, D.M. Positive allosteric modulator of the human 5-HT2C receptor. Mol. Pharmacol., 2003, 64(1), 78-84.
[] [PMID: 12815163]
Spízek, J.; Novotná, J.; Rezanka, T. Lincosamides: chemical structure, biosynthesis, mechanism of action, resistance, and applications. Adv. Appl. Microbiol., 2004, 56, 121-154.
[] [PMID: 15566978]
Ding, C.; Bremer, N.M.; Smith, T.D.; Seitz, P.K.; Anastasio, N.C.; Cunningham, K.A.; Zhou, J. Exploration of synthetic approaches and pharmacological evaluation of PNU-69176E and its stereoisomer as 5-HT2C receptor allosteric modulators. ACS Chem. Neurosci., 2012, 3(7), 538-545.
[] [PMID: 22860223]
Sugiura, T.; Kondo, S.; Kodaka, T.; Tonegawa, T.; Nakane, S.; Yamashita, A.; Ishima, Y.; Waku, K. Enzymatic synthesis of oleamide (cis-9, 10-octadecenoamide), an endogenous sleep-inducing lipid, by rat brain microsomes. Biochem. Mol. Biol. Int., 1996, 40(5), 931-938.
[PMID: 8955882]
Boger, D.L.; Sato, H.; Lerner, A.E.; Austin, B.J.; Patterson, J.E.; Patricelli, M.P.; Cravatt, B.F. Trifluoromethyl ketone inhibitors of fatty acid amide hydrolase: a probe of structural and conformational features contributing to inhibition. Bioorg. Med. Chem. Lett., 1999, 9(2), 265-270.
[] [PMID: 10021942]
Fedorova, I.; Hashimoto, A.; Fecik, R.A.; Hedrick, M.P.; Hanus, L.O.; Boger, D.L.; Rice, K.C.; Basile, A.S. Behavioral evidence for the interaction of oleamide with multiple neurotransmitter systems. J. Pharmacol. Exp. Ther., 2001, 299(1), 332-342.
[PMID: 11561096]
Soria-Gómez, E.; Márquez-Diosdado, M.I.; Montes-Rodríguez, C.J.; Estrada-González, V.; Prospéro-García, O. Oleamide administered into the nucleus accumbens shell regulates feeding behaviour via CB1 and 5-HT2C receptors. Int. J. Neuropsychopharmacol., 2010, 13(9), 1247-1254.
[] [PMID: 20663269]
Boger, D.L.; Patterson, J.E.; Jin, Q. Structural requirements for 5-HT2A and 5-HT1A serotonin receptor potentiation by the biologically active lipid oleamide. Proc. Natl. Acad. Sci. USA, 1998, 95(8), 4102-4107.
[] [PMID: 9539697]
Huidobro-Toro, J.P.; Harris, R.A. Brain lipids that induce sleep are novel modulators of 5-hydroxytrypamine receptors. Proc. Natl. Acad. Sci. USA, 1996, 93(15), 8078-8082.
[] [PMID: 8755606]
Thomas, E.A.; Carson, M.J.; Neal, M.J.; Sutcliffe, J.G. Unique allosteric regulation of 5-hydroxytryptamine receptor-mediated signal transduction by oleamide. Proc. Natl. Acad. Sci. USA, 1997, 94(25), 14115-14119.
[] [PMID: 9391162]
Hedlund, P.B.; Carson, M.J.; Sutcliffe, J.G.; Thomas, E.A. Allosteric regulation by oleamide of the binding properties of 5-hydroxytryptamine7 receptors. Biochem. Pharmacol., 1999, 58(11), 1807-1813.
[] [PMID: 10571256]
Cheer, J.F.; Cadogan, A.K.; Marsden, C.A.; Fone, K.C.; Kendall, D.A. Modification of 5-HT2 receptor mediated behaviour in the rat by oleamide and the role of cannabinoid receptors. Neuropharmacology, 1999, 38(4), 533-541.
[] [PMID: 10221757]
García-Cárceles, J.; Decara, J.M.; Vázquez-Villa, H.; Rodríguez, R.; Codesido, E.; Cruces, J.; Brea, J.; Loza, M.I.; Alén, F.; Botta, J.; McCormick, P.J.; Ballesteros, J.A.; Benhamú, B.; Rodríguez de Fonseca, F.; López-Rodríguez, M.L. A positive allosteric modulator of the serotonin 5-HT2C receptor for obesity. J. Med. Chem., 2017, 60(23), 9575-9584.
[] [PMID: 29116785]
Singh, K.; Sona, C.; Ojha, V.; Singh, M.; Mishra, A.; Kumar, A.; Siddiqi, M.I.; Tripathi, R.P.; Yadav, P.N. Identification of dual role of piperazine-linked phenyl cyclopropyl methanone as positive allosteric modulator of 5-HT2C and negative allosteric modulator of 5-HT2B receptors. Eur. J. Med. Chem., 2019, 164, 499-516.
[] [PMID: 30622024]
Mikitsh, J.L.; Chacko, A.M. Pathways for small molecule delivery to the central nervous system across the blood-brain barrier. Perspect. Medicin. Chem., 2014, 6, 11-24.
[] [PMID: 24963272]
Marona-Lewicka, D.; Nichols, D.E. Complex stimulus properties of LSD: a drug discrimination study with alpha 2-adrenoceptor agonists and antagonists. Psychopharmacology (Berl.), 1995, 120(4), 384-391.
[] [PMID: 8539318]
Kleven, M.S.; Assié, M.B.; Koek, W. Pharmacological characterization of in vivo properties of putative mixed 5-HT1A agonist/5-HT(2A/2C) antagonist anxiolytics. II. Drug discrimination and behavioral observation studies in rats. J. Pharmacol. Exp. Ther., 1997, 282(2), 747-759.
[PMID: 9262338]
Mohler, E.G.; Franklin, S.R.; Rueter, L.E. Discriminative-stimulus effects of NS9283, a nicotinic α4β2* positive allosteric modulator, in nicotine-discriminating rats. Psychopharmacology (Berl.), 2014, 231(1), 67-74.
[] [PMID: 23925734]
Ward, R.J.; Pediani, J.D.; Godin, A.G.; Milligan, G. Regulation of oligomeric organization of the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor observed by spatial intensity distribution analysis. J. Biol. Chem., 2015, 290(20), 12844-12857.
[] [PMID: 25825490]

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Year: 2019
Published on: 15 September, 2019
Page: [1381 - 1398]
Pages: 18
DOI: 10.2174/1568026619666190709101449
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