Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

Pharmacological Research

Volumn 106, Issue , 2016, Pages 51-63

  Lian, Jiamei ^a,b   Huang, Xu Feng ^a,b   Pai, Nagesh ^b   Deng, Chao ^a,b  

^a ILLAWARRA HEALTH AND MEDICAL RESEARCH INSTITUTE   (Australia)

^b UNIVERSITY OF WOLLONGONG   (Australia)

Author keywords

Antipsychotic drug; Betahistine; Histamine receptor; Locomotor activity; Therapeutic efficacy; Weight gain

Indexed keywords

BETAHISTINE; CLOZAPINE; COCAINE AND AMPHETAMINE REGULATED TRANSCRIPT PEPTIDE; DOPAMINE 2 RECEPTOR; HISTAMINE H1 RECEPTOR; HISTAMINE H3 RECEPTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE ALPHA; NEUROLEPTIC AGENT; NEUROPEPTIDE Y; OLANZAPINE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PLACEBO; PROOPIOMELANOCORTIN; QUETIAPINE; REBOXETINE; RISPERIDONE; SEROTONIN RECEPTOR; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; UNCLASSIFIED DRUG; BENZODIAZEPINE DERIVATIVE; HISTAMINE AGONIST;

BRAIN REGION; BROWN ADIPOSE TISSUE; DISEASE ASSOCIATION; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG EXPOSURE; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG SAFETY; DYSLIPIDEMIA; ENERGY BALANCE; FOOD INTAKE; HUMAN; LOCOMOTION; MENTAL DISEASE; METABOLIC REGULATION; NEUROTRANSMISSION; NONHUMAN; OBESITY; OUTCOME ASSESSMENT; PATHOGENESIS; POLYPHARMACY; PRIORITY JOURNAL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECEPTOR UPREGULATION; REVIEW; SCHIZOPHRENIA; SIDE EFFECT; SIGNAL TRANSDUCTION; SYSTEMATIC REVIEW; THERMOGENESIS; TREATMENT DURATION; WEIGHT GAIN; ANIMAL; DRUG EFFECTS; METABOLISM;

AMP-ACTIVATED PROTEIN KINASES; ANIMALS; ANTIPSYCHOTIC AGENTS; BENZODIAZEPINES; BETAHISTINE; HISTAMINE AGONISTS; HUMANS; RECEPTORS, HISTAMINE H1; WEIGHT GAIN;

EID: 84959139148     PISSN: 10436618     EISSN: 10961186     Source Type: Journal    
DOI: 10.1016/j.phrs.2016.02.011     Document Type: Review

References (203)

1. J.M. Kane, and C.U. Correll Past and present progress in the pharmacologic treatment of schizophrenia J. Clin. Psychiatry 71 2010 1115 1124
2. R.A. Krill, and S. Kumra Metabolic consequences of second-generation antipsychotics in youth: appropriate monitoring and clinical management Adolesc. Health Med. Ther. 5 2014 171 182
3. T. Lambert Managing the metabolic adverse effects of antipsychotic drugs in patients with psychosis Aust. Prescr. 34 2011 97 99
4. H.Y. Meltzer Update on typical and atypical antipsychotic drugs Annu. Rev. Med. 64 2013 393 406
5. C. Cuerda, C. Velasco, J. Merchan-Naranjo, P. Garcia-Peris, and C. Arango The effects of second-generation antipsychotics on food intake: resting energy expenditure and physical activity Eur. J. Clin. Nutr. 68 2014 146 152
6. C. Deng Effects of antipsychotic medications on appetite weight, and insulin resistance Endocrinol. Metab. Clin. North Am. 42 2013 545 563
7. W. Milano, M. De Rosa, L. Milano, and A. Capasso Antipsychotic drugs opposite to metabolic risk: neurotransmitters: neurohormonal and pharmacogenetic mechanisms underlying with weight gain and metabolic syndrome Open Neurol. J. 7 2013 23 31
8. C.U. Correll, T. Lencz, and A.K. Malhotra Antipsychotic drugs and obesity Trends Mol. Med. 17 2011 97 107
9. O. Osuntokun, B. Millen, W.I. Xu, L.A. Kryzhanovskaya, C. Robertson-Plouch, J.L. Carlson, N. Acharya, and S.A. Corya Metabolic parameters in patients treated with olanzapine or other atypical antipsychotics J. Psychopharmacol. (Oxf.) 25 2011 630 638
10. N. Warikoo, S. Chakrabarti, and S. Grover Adherence and continuation of treatment with first- and second-generation antipsychotics in schizophrenia Indian J. Psychol. Med. 36 2014 33 39
11. L.W. Harris, P.C. Guest, M.T. Wayland, Y. Umrania, D. Krishnamurthy, H. Rahmoune, and S. Bahn Schizophrenia: metabolic aspects of aetiology: diagnosis and future treatment strategies Psychoneuroendocrinology 38 2013 752 766
12. 3 receptors in food intake: a mechanism for atypical antipsychotic-induced weight gain Prog. Neuropsychopharmacol. Biol. Psychiatry. 34 2010 1 4
13. 1 receptor antagonism in antipsychotic-induced weight gain CNS Drugs 27 2013 423 434
14. 1-Histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs Neuropsychopharmacology 28 2003 519 526
15. C. Attux, L.C. Martini, C.M. d. Araújo, A.M. Roma, A.F. Reis, and R.A. Bressan The effectiveness of a non-pharmacological intervention for weight gain management in severe mental disorders: results from a national multicentric study Rev. Bras. Psiquiatr. 33 2011 117 121
16. G. Faulkner, T.A. Cohn, Pharmacologic and nonpharmacologic strategies for weight gain and metabolic disturbance in patients treated with antipsychotic medications.[erratum appears in Can J Psychiatry. 2006 Aug; 51 (9): 620]. Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie 51 (2006) 502-511.
17. J.G. Fiedorowicz, D.D. Miller, J.R. Bishop, C.A. Calarge, V.L. Ellingrod, and W.G. Haynes Systematic review and meta-analysis of pharmacological interventions for weight gain from antipsychotics and mood stabilizers Curr. Psychiatry Rev. 8 2012 25 36
18. T. Baptista, Y. ElFakih, E. Uzcátegui, I. Sandia, E. Tálamo, E. Araujo De Baptista, and S. Beaulieu Pharmacological management of atypical antipsychotic-induced weight gain CNS Drugs 22 2008 477 495
19. L. Maayan, J. Vakhrusheva, and C.U. Correll Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis Neuropsychopharmacology 35 2010 1520 1530
20. L.F. Jarskog, R.M. Hamer, D.J. Catellier, D.D. Stewart, L. LaVange, N. Ray, L.H. Golden, J.A. Lieberman, T.S. Stroup, L. Adler, G. Burnie, M. Barber, M. Byerly, J.M. Canive, I. Glick, D.C. Henderson, J.S. Lamberti, A. Khan, J.P. McEvoy, H. Meltzer, A. Miller, D.D. Miller, H.A. Nasrallah, S. Olson, J.K. Patel, and B.L. Saltz Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder Am. J. Psychiatry 170 2013 1032 1040
21. J.A. Morrison, E.M. Cottingham, and B.A. Barton Metformin for weight loss in pediatric patients taking psychotropic drugs Am. J. Psychiatry 159 2002 655 657
22. L. Shin, H. Bregman, J.L. Breeze, N. Noyes, and J.A. Frazier Metformin for weight control in pediatric patients on atypical antipsychotic medication J. Child Adolesc. Psychopharmacol. 19 2009 275 279
23. L.A. Weaver, D.D. De Leon, K. Borgmann-Winter, and B.J. Coffey Use of metformin to control clozapine-associated weight gain in an adolescent with schizoaffective disorder J. Child Adolesc. Psychopharmacol. 20 2010 153 157
24. Y. Hu, A.J. Young, E.A. Ehli, D. Nowotny, P.S. Davies, E.A. Droke, T.J. Soundy, and G.E. Davies Metformin and berberine prevent olanzapine-induced weight gain in rats PLoS One 9 2014 e93310
25. T. Baptista, N. Rangel, Y. El Fakih, E. Uzcategui, T. Galeazzi, S. Beaulieu, and E. Araujo de Baptista Rosiglitazone in the assistance of metabolic control during olanzapine administration in schizophrenia: a pilot double-blind placebo-controlled, 12-week trial Pharmacopsychiatry 42 2009 14 19
26. M. Ehret, J. Goethe, M. Lanosa, and C.I. Coleman The effect of metformin on anthropometrics and insulin resistance in patients receiving atypical antipsychotic agents: a meta-analysis J. Clin. Psychiatry 71 2010 1286 1292
27. F. Biedermann Sibutramine in the treatment of antipsychotic-induced weight gain: a pilot study in patients with schizophrenia Int. Clin. Psychopharmacol. 29 2014 181 184
28. C. Das, G. Mendez, S. Jagasia, and L.A. Labbate Second-generation antipsychotic use in schizophrenia and associated weight gain: a critical review and meta-analysis of behavioral and pharmacologic treatments Ann. Clin. Psychiatry 24 2012 225 239
29. J.P. Domecq, G. Prutsky, A. Leppin, M.B. Sonbol, O. Altayar, C. Undavalli, Z. Wang, T. Elraiyah, J.P. Brito, K.F. Mauck, M.H. Lababidi, L.J. Prokop, N. Asi, J. Wei, S. Fidahussein, V.M. Montori, and M.H. Murad Clinical review: drugs commonly associated with weight change: a systematic review and meta-analysis J. Clin. Endocrinol. Metab. 100 2015 363 370
30. J.A. Generali, and D.J. Cada Topiramate: antipsychotic-induced weight gain Hosp. Pharm. 49 2014 345 347
31. A. Ghanizadeh, M.S. Nikseresht, and A. Sahraian The effect of zonisamide on antipsychotic-associated weight gain in patients with schizophrenia: a randomized double-blind, placebo-controlled clinical trial Schizophr. Res. 147 2013 110 115
32. Y. Mizuno, T. Suzuki, A. Nakagawa, K. Yoshida, M. Mimura, W.W. Fleischhacker, and H. Uchida Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis Schizophr. Bull. 2014 10.1093/schbul/sbu030
33. G. Provensi, P. Blandina, and M.B. Passani The histaminergic system as a target for the prevention of obesity and metabolic syndrome Neuropharmacology 2015 1 10
34. H.L. Haas, O.A. Sergeeva, and O. Selbach Histamine in the nervous system Physiol. Rev. 88 2008 1183 1241
35. T. Masaki, and H. Yoshimatsu Neuronal histamine and its receptors: implication of the pharmacological treatment of obesity Curr. Med. Chem. 17 2010 4587 4592
36. E.A. Jorgensen, T.W. Vogelsang, U. Knigge, T. Watanabe, J. Warberg, and A. Kjaer Increased susceptibility to diet-induced obesity in histamine-deficient mice Neuroendocrinology 83 2006 289 294
37. R.E. Brown, D.R. Stevens, and H.L. Haas The physiology of brain histamine Prog. Neurobiol. 63 2001 637 672
38. T. Masaki, and H. Yoshimatsu The hypothalamic H1 receptor: a novel therapeutic target for disrupting diurnal feeding rhythm and obesity Trends Pharmacol. Sci. 27 2006 279 284
39. L-histidine decarboxylase expression and local upregulation in limbic seizures Eur. J. Neurosci. 10 1998 2287 2301
40. 3) of histamine receptor Nature 302 1983 832 837
41. 4 receptors in the central nervous system of human and rat Brain Res. 1250 2009 41 48
42. 3 receptor and eating behavior J. Pharmacol. Exp. Ther. 336 2011 24 29
43. 2A receptors and 5-HT transporters in diet-induced obese rats Brain Res. 847 1999 90 97
44. J. Sethi, M. Sanchez-Alavez, and I.V. Tabarean Loss of histaminergic modulation of thermoregulation and energy homeostasis in obese mice Neuroscience 217 2012 84 95
45. B.V. Clineschmidt, and V.J. Lotti Histamine: intraventricular injection suppresses ingestive behavior of the cat Arch. Int. Pharmacodyn. Ther. 206 1973 288 298
46. N. Itowi, K. Nagai, H. Nakagawa, T. Watanabe, and H. Wada Changes in the feeding behavior of rats elicited by histamine infusion Physiol. Behav. 44 1988 221 226
47. 3 agonists on food and water intake and urine flow in Wistar rats Brain Res. 793 1998 279 288
48. A.K. Fulop, A. Foldes, E. Buzas, K. Hegyi, I.H. Miklos, L. Romics, M. Kleiber, A. Nagy, A. Falus, and K.J. Kovacs Hyperleptinemia visceral adiposity, and decreased glucose tolerance in mice with a targeted disruption of the histidine decarboxylase gene Endocrinology 144 2003 4306 4314
49. K.-Y. Wang, A. Tanimoto, S. Yamada, X. Guo, Y. Ding, T. Watanabe, T. Watanabe, K. Kohno, K.-I. Hirano, H. Tsukada, and Y. Sasaguri Histamine regulation in glucose and lipid metabolism via histamine receptors: model for nonalcoholic steatohepatitis in mice Am. J. Pathol. 177 2010 713 723
50. N. Davoodi, M. Kalinichev, and P.G. Clifton Comparative effects of olanzapine and ziprasidone on hypophagia induced by enhanced histamine neurotransmission in the rat Behav. Pharmacol. 19 2008 121 128
51. 1 Receptor in the regulation of feeding rhythm and obesity Diabetes 53 2004 2250 2260
52. S.L. Poole, D.I. Lewis, and S.A. Deuchars Histamine depolarizes neurons in the dorsal vagal complex Neurosci. Lett. 432 2008 19 24
53. 2c serotonin receptors Nature 374 1995 542 546
54. T. Masaki, H. Yoshimatsu, S. Chiba, T. Watanabe, and T. Sakata Targeted disruption of histamine H1-receptor attenuates regulatory effects of leptin on feeding adiposity, and UCP family in mice Diabetes 50 2001 385 391
55. H. Umehara, H. Mizuguchi, N. Mizukawa, M. Matsumoto, N. Takeda, E. Senba, and H. Fukui Innervation of histamine neurons in the caudal part of the arcuate nucleus of hypothalamus and their activation in response to food deprivation under scheduled feeding Methods Find. Exp. Clin. Pharmacol. 32 2010 733 736
56. M. He, Q. Zhang, C. Deng, H. Wang, J. Lian, and X.-F. Huang Hypothalamic histamine H1 receptor-AMPK signaling time-dependently mediates olanzapine-induced hyperphagia and weight gain in female rats Psychoneuroendocrinology 42 2014 153 164
57. R. Coccurello, and A. Moles Potential mechanisms of atypical antipsychotic-induced metabolic derangement: clues for understanding obesity and novel drug design Pharmacol. Ther. 127 2010 210 251
58. C. Correll Monitoring and management of antipsychotic-related metabolic and endocrine adverse events in pediatric patients Int. Rev. Psychiatry 20 2008 195 201
59. A. Matsui-Sakata, H. Ohtani, and Y. Sawada Receptor occupancy-based analysis of the contributions of various receptors to antipsychotics-induced weight gain and diabetes mellitus Drug Metab. Pharmacokinet. 20 2005 368 378
60. F. Panariello, V. De Luca, and A. de Bartolomeis Weight gain, schizophrenia and antipsychotics: new findings from animal model and pharmacogenomic studies Schizophr. Res. Treat. 2011 2011 459284
61. S. Stahl, J. Meyer, and L. Mignon Which comes first: atypical antipsychotic treatment or cardiometabolic risk Acta Psychiatr. Scand. 119 2009 171 179
62. 1 receptor expression Psychoneuroendocrinology 33 2008 569 580
63. 1 receptor-linked activation of hypothalamic AMP-kinase Proc. Natl. Acad. Sci. U.S.A. 104 2007 3456 3459
64. J. Lian, X.-F. Huang, N. Pai, and C. Deng Betahistine ameliorates olanzapine-induced weight gain through modulation of histaminergic: nPY and AMPK pathways Psychoneuroendocrinology 48 2014 77 86
65. J. Lian, X.-F. Huang, N. Pai, and C. Deng Preventing olanzapine-induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment PLoS One 9 2014 e104160
66. 3 receptors with BMI and HbA1c values in patients on antipsychotic medication Psychopharmacology (Berl.) 216 2011 257 265
67. A. WysokinskiI, and I. Kloszewska Mechanisms of increased appetite and weight gain induced by psychotropic medications J. Adv. Clin. Pharmacol. 1 2014 12 33
68. S. Erhart, S. Marder, and B. Spellberg Novel antipsychotics and new onset diabetes Biol. Psychiatry 44 1998 778 783
69. D.A. Wirshing, W.C. Wirshing, L. Kysar, M.A. Berisford, D. Goldstein, J. Pashdag, J. Mintz, and S.R. Marder Novel antipsychotics: comparison of weight gain liabilities J. Clin. Psychiatry 60 1999 358 363
70. P. Chervinsky, J. Georgitis, C. Banov, P. Boggs, R. Vande Souwe, and S. Greenstein Once daily loratadine versus astemizole once daily Ann. Allergy 73 1994 109 113
71. J.W. Saleh, M.U. Yang, T.B. van Itallie, and S.A. Hashim Ingestive behavior and composition of weight change during cyproheptadine administration Int. J. Obes. 3 1979 213 221
72. A.M. Sant'Anna, P.S. Hammes, M. Porporino, C. Martel, C. Zygmuntowicz, and M. Ramsay Use of cyproheptadine in young children with feeding difficulties and poor growth in a pediatric feeding program J. Pediatr. Gastroenterol. Nutr. 59 2014 674 678
73. T. Silverstone, and D. Schuyler The effect of cyproheptadine on hunger: calorie intake and body weight in man Psychopharmacologia 40 1975 335 340
74. G. Jassim, S. Skrede, M. Vázquez, H. Wergedal, A. Vik-Mo, N. Lunder, C. Diéguez, A. Vidal-Puig, R. Berge, M. López, and V.J. Steen Fernø Acute effects of orexigenic antipsychotic drugs on lipid and carbohydrate metabolism in rat Psychopharmacology (Berl.) 219 2012 783 794
75. X. Liu, J. Lian, C.H. Hu, and C. Deng Betahistine co-treatment ameliorates dyslipidemia induced by chronic olanzapine treatment in rats through modulation of hepatic AMPKalpha-SREBP-1 and PPARalpha-dependent pathways Pharmacol. Res. 100 2015 36 46
76. E.G. Lundius, M. Sanchez-Alavez, Y. Ghochani, J. Klaus, and I.V. Tabarean Histamine influences body temperature by acting at H1 and H3 receptors on distinct populations of preoptic neurons J. Neurosci. 30 2010 4369 4381
77. K.L. Teff, and S.F. Kim Atypical antipsychotics and the neural regulation of food intake and peripheral metabolism Physiol. Behav. 104 2011 590 598
78. P. Panula, and S. Nuutinen The histaminergic network in the brain: basic organization and role in disease Nat. Rev. Neurosci. 14 2013 4724 4787
79. C. Pillot, A. Heron, V. Cochois, J. Tardivel-Lacombe, X. Ligneau, J.C. Schwartz, and J.M. Arrang A detailed mapping of the histamine H3 receptor and its gene transcripts in rat brain Neuroscience 114 2002 173 193
80. 3 receptors results in changes in brain histamine tone leading to an obese phenotype J. Clin. Invest. 110 2002 1791 1799
81. 3 receptors inhibit serotonin release in substantia nigra pars reticulata J. Neurosci. 24 2004 8704 8710
82. E. SchlickerI. Marr. The moderate affinity of clozapine at H₃ receptors is not shared by its two major metabolites and by structurally related and unrelated atypical neuroleptics. Naunyn Schmiedebergs Arch Pharmacol, 353 (1996) 290-294.
83. D. Vohora, and M. Bhowmik Histamine H3 receptor antagonists/inverse agonists on cognitive and motor processes: relevance to Alzheimer's disease ADHD, schizophrenia, and drug abuse Front. Syst. Neurosci. 6 2012 72
84. 3 autoreceptors modulate histamine synthesis through cAMP pathway Mol. Pharmacol. 61 2002 239 245
85. S. Chiba, E. Itateyama, T. Sakata, and H. Yoshimatsu Acute central administration of immepip a histamine H3 receptor agonist, suppresses hypothalamic histamine release and elicits feeding behavior in rats Brain Res. Bull. 79 2009 37 40
86. T. Murotani, T. Ishizuka, Y. Isogawa, M. Karashima, and A. Yamatodani Possible involvement of serotonin 5-HT2 receptor in the regulation of feeding behavior through the histaminergic system Neuropharmacology 61 2011 228 233
87. D. Kohno, H. Sone, S. Tanaka, H. Kurita, D. Gantulga, and T. Yada AMP-activated protein kinase activates neuropeptide Y neurons in the hypothalamic arcuate nucleus to increase food intake in rats Neurosci. Lett. 499 2011 194 198
88. Y. Minokoshi, T. Alquier, N. Furukawa, Y.-B. Kim, A. Lee, B. Xue, J. Mu, F. Foufelle, P. Ferre, M.J. Birnbaum, B.J. Stuck, and B.B. Kahn AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus Nature 428 2004 569 574
89. T.L. Martin, T. Alquier, K. Asakura, N. Furukawa, F. Preitner, and B.B. Kahn Diet-induced obesity alters AMP kinase activity in hypothalamus and skeletal muscle J. Biol. Chem. 281 2006 18933 18941
90. B.B. Kahn, T. Alquier, D. Carling, and D.G. Hardie AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism Cell Metab. 1 2005 15 25
91. B. Kola Role of AMP-activated protein kinase in the control of appetite J. Neuroendocrinol. 20 2008 942 951
92. R. Lage, C. Dieguez, A. Vidal-Puig, and M. Lopez AMPK: a metabolic gauge regulating whole-body energy homeostasis Trends Mol. Med. 14 2008 539 549
93. S. Ramírez, L. Martins, J. Jacas, P. Carrasco, M. Pozo, J. Clotet, D. Serra, F.G. Hegardt, C. Diéguez, M. López, and N. Casals Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin Diabetes 62 2013 2329 2337
94. G.V. Ronnett, S. Ramamurthy, A.M. Kleman, L.E. Landree, and S. Aja AMPK in the brain: its roles in energy balance and neuroprotection J. Neurochem. 109 Suppl. 1 2009 17 23
95. 2+ signaling in rat hypothalamic cells PLoS One 7 2012 e36185
96. E. Sejima, A. Yamauchi, T. Nishioku, M. Koga, K. Nakagama, S. Dohgu, K. Futagami, and Y. Kataoka A role for hypothalamic AMP-activated protein kinase in the mediation of hyperphagia and weight gain induced by chronic treatment with olanzapine in female rats Cell. Mol. Neurobiol. 31 2011 985 989
97. S. Skrede, L. Martins, R.K. Berge, V.M. Steen, M. López, and J. Ferno Olanzapine depot formulation in rat: A step forward in modelling antipsychotic-induced metabolic adverse effects Int. J. Neuropsychopharmacol. 17 2014 91 104
98. J. Fernø, L. Varela, S. Skrede, M.J. Vázquez, R. Nogueiras, C. Diéguez, A. Vidal-Puig, V.M. Steen, and M. López Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation PLoS One 6 2011 e20571
99. P.J.F. Martins, M. Haas, and S. Obici Central nervous system delivery of the antipsychotic olanzapine induces hepatic insulin resistance Diabetes 59 2010 2418 2425
100. M. Ak, D. Sezlev, L. Sutcigil, S. Akarsu, F. Ozgen, and T. Yanik The investigation of leptin and hypothalamic neuropeptides role in first attack psychotic male patients: olanzapine monotherapy Psychoneuroendocrinology 38 2013 341 347
101. A. Joly-Amado, C. Cansell, R.G.P. Denis, A.-S. Delbes, J. Castel, S. Martinez, and S. Luquet The hypothalamic arcuate nucleus and the control of peripheral substrates Best Pract. Res. Clin. Endocrinol. Metab. 28 2014 725 737
102. C. Sobrino Crespo, A. Perianes Cachero, L. Puebla Jiménez, V. Barrios, and E. Arilla Ferreiro Peptides and food intake Front. Endocrinol. 5 2014 58
103. W. Zhang, M.A. Cline, and E.R. Gilbert Hypothalamus-adipose tissue crosstalk: Neuropeptide y and the regulation of energy metabolism Nutr. Metab. (Lond.) 11 2014
104. R.L. Bradley, J.P.R. Mansfield, and E. Maratos-Flier Neuropeptides, including neuropeptide Y and melanocortins: mediate lipolysis in murine adipocytes Obes. Res. 13 2005 653 661
105. S.P. Brothers, and C. Wahlestedt Therapeutic potential of neuropeptide Y (NPY) receptor ligands EMBO Mol. Med. 2 2010 429 439
106. D. Larhammar, A.G. Blomqvist, and C. Soderberg Evolution of neuropeptide Y and its related peptides Comp. Biochem. Physiol. C 106 1993 743 752
107. M. George, M. Rajaram, and E. Shanmugam New and emerging drug molecules against obesity J. Cardiovasc. Pharmacol. Ther. 19 2014 65 76
108. H. Ziauddeen, and P.C. Fletcher Central nervous system biomarkers for antiobesity drug development Drug Discov. Today 18 2013 1282 1291
109. B.G. Stanley, and W.J. Thomas Feeding responses to perifornical hypothalamic injection of neuropeptide Y in relation to circadian rhythms of eating behavior Peptides 14 1993 475 481
110. K. Suzuki, C.N. Jayasena, and S.R. Bloom Obesity and appetite control Exp. Diabetes Res. 2012 824305
111. S.F. Leibowitz, and K.E. Wortley Hypothalamic control of energy balance: different peptides different functions Peptides 25 2004 473 504
112. R.E. Mercer, M.J. Chee, and W.F. Colmers The role of NPY in hypothalamic mediated food intake Front. Neuroendocrinol. 32 2011 398 415
113. W. Zhang, M. Cline, and E. Gilbert Hypothalamus-adipose tissue crosstalk: neuropeptide Y and the regulation of energy metabolism Nutr. Metab. 11 2014 27
114. D. Kohno, and T. Yada Arcuate NPY neurons sense and integrate peripheral metabolic signals to control feeding Neuropeptides 46 2012 315 319
115. S. Stanley, K. Wynne, B. McGowan, and S. Bloom Hormonal regulation of food intake Physiol. Rev. 85 2005 1131 1158
116. J.R. Barson, I. Morganstern, and S.F. Leibowitz Neurobiology of consummatory behavior: mechanisms underlying overeating and drug use ILAR J. 53 2012 35 58
117. C. Broberger, J. Johansen, C. Johansson, M. Schalling, and T. Hokfelt The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal anorectic, and monosodium glutamate-treated mice Proc. Natl. Acad. Sci. U. S. A. 95 1998 15043 15048
118. R. Cone Anatomy and regulation of the central melanocortin system Nat. Neurosci. 8 2005 571 578
119. C. Haskell-Luevano, P. Chen, C. Li, K. Chang, M. Smith, J. Cameron, and R. Cone Characterization of the neuroanatomical distribution of agouti-related protein immunoreactivity in the rhesus monkey and the rat Endocrinology 140 1999 1408 1415
120. W. Nijenhuis, J. Oosterom, and R. Adan AgRP (83-132) acts as an inverse agonist on the human-melanocortin-4 receptor Mol. Endocrinol. 15 2001 164 171
121. D.L. Marks, N. Boucher, C.M. Lanouette, L. Perusse, G. Brookhart, A.G. Comuzzie, Y.C. Chagnon, and R.D. Cone Ala67Thr polymorphism in the Agouti-related peptide gene is associated with inherited leanness in humans Am. J. Med. Genet. A 126A 2004 267 271
122. C. Bjørbæk Central leptin receptor action and resistance in obesity J. Investig. Med. 57 2009 789 794
123. M. Ollmann, B. Wilson, Y.-K. Yang, J. Kerns, Y. Chen, I. Gantz, and G. Barsh Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein Science 278 1997 135 138
124. J.R. Shutter, M. Graham, A.C. Kinsey, S. Scully, R. Luthy, and K.L. Stark Hypothalamic expression of ART a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice Genes Dev. 11 1997 593 602
125. M.M. Hagan, P.A. Rushing, L.M. Pritchard, M.W. Schwartz, A.M. Strack, L.H. Van Der Ploeg, S.C. Woods, and R.J. Seeley Long-term orexigenic effects of AgRP-(83 - 132) involve mechanisms other than melanocortin receptor blockade Am. J. Physiol. Regul. Integr. Comp. Physiol. 279 2000 R47 52
126. M.W. Schwartz, S.C. Woods, D. Porte Jr., R.J. Seeley, and D.G. Baskin Central nervous system control of food intake Nature 404 2000 661 671
127. E. Gropp, M. Shanabrough, E. Borok, A.W. Xu, R. Janoschek, T. Buch, L. Plum, N. Balthasar, B. Hampel, A. Waisman, G.S. Barsh, T.L. Horvath, and J.C. Bruning Agouti-related peptide-expressing neurons are mandatory for feeding Nat. Neurosci. 8 2005 1289 1291
128. K. Weston-Green, X.F. Huang, and C. Deng Alterations to melanocortinergic GABAergic and cannabinoid neurotransmission associated with olanzapine PLoS One 7 2012 e33548
129. Q. Zhang, M. He, C. Deng, H. Wang, J. Lian, and X.F. Huang Hypothalamic ghrelin signalling mediates olanzapine-induced hyperphagia and weight gain in female rats Int. J. Neuropsychopharmacol. 17 2014 807 818
130. G. Nikisch, P. Baumann, T. Liu, and A.A. Mathe Quetiapine affects neuropeptide Y and corticotropin-releasing hormone in cerebrospinal fluid from schizophrenia patients: relationship to depression and anxiety symptoms and to treatment response Int. J. Neuropsychopharmacol. 15 2012 1051 1061
131. S.L. Kirk, M. Cahir, and G.P. Reynolds Clozapine but not haloperidol, increases neuropeptide Y neuronal expression in the rat hypothalamus J. Psychopharmacol. (Oxf.) 20 2006 577 579
132. S. Ehrlich, K. Leopold, J.V. Merle, I. Theophil, W. Haag, M. Lautenschlager, and M. Schaefer Trajectories of agouti-related protein and leptin levels during antipsychotic-associated weight gain in patients with schizophrenia J. Clin. Psychopharmacol. 32 2012 767 772
133. G. Ruano, J.W. Goethe, C. Caley, S. Woolley, T.R. Holford, M. Kocherla, A. Windemuth, and J. de Leon Physiogenomic comparison of weight profiles of olanzapine- and risperidone-treated patients Mol. Psychiatry 12 2007 474 482
134. A.K. Tiwari, E.J. Brandl, C. Weber, O. Likhodi, C.C. Zai, M.K. Hahn, J.A. Lieberman, H.Y. Meltzer, J.L. Kennedy, and D.J. Muller Association of a functional polymorphism in neuropeptide Y with antipsychotic-induced weight gain in schizophrenia patients J. Clin. Psychopharmacol. 33 2013 11 17
135. E.A. Jorgensen, U. Knigge, T. Watanabe, J. Warberg, and A. Kjaer Histaminergic neurons are involved in the orexigenic effect of orexin-A Neuroendocrinology 82 2005 70 77
136. G.J. MortonM.W. Schwartz The NPY/AgRP neuron and energy homeostasis Int. J. Obes. Relat. Metab. Disord. 25 2001 S56 62
137. A. Slominski, J. Wortsman, T. Luger, R. Paus, and S. Solomon Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress Physiol. Rev. 80 2000 979 1020
138. G. Millington Pro-opiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors Clin. Exp. Dermatol. 31 2006 407 412
139. H.B. Patel, T. Montero-Melendez, K.V. Greco, and M. Perretti Melanocortin receptors as novel effectors of macrophage responses in inflammation Front. Immunol. 2 2011 41
140. D. Wang, X. He, Z. Zhao, Q. Feng, R. Lin, Y. Sun, T. Ding, F. Xu, M. Luo, and C. Zhan Whole-brain mapping of the direct inputs and axonal projections of POMC and AgRP neurons Front. Neuroanat. 9 2015 40
141. E. Jobst, P. Enriori, and M. Cowley The electrophysiology of feeding circuits Trends Endocrinol. Metab. 15 2004 488 499
142. M. Baker, N. Gaukrodger, B.M. Mayosi, H. Imrie, M. Farrall, H. Watkins, J.M. Connell, P.J. Avery, and B. Keavney Association between common polymorphisms of the proopiomelanocortin gene and body fat distribution: a family study Diabetes 54 2005 2492 2496
143. A. Ternouth, M.K. Brandys, Y.T. van der Schouw, J. Hendriks, J.O. Jansson, D. Collier, and R.A. Adan Association study of POMC variants with body composition measures and nutrient choice Eur. J. Pharmacol. 660 2011 220 225
144. L. Yaswen, N. Diehl, M. Brennan, and U. Hochgeschwender Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin Nat. Med. 5 1999 1066 1070
145. M.M. Hagan, P.A. Rushing, M.W. Schwartz, K.A. Yagaloff, P. Burn, S.C. Woods, and R.J. Seeley Role of the CNS melanocortin system in the response to overfeeding J. Neurosci. 19 1999 2362 2367
146. G. Millington The role of proopiomelanocortin (POMC) neurones in feeding behaviour Nutr. Metab. 4 2007 18
147. G.P. Reynolds, and S.L. Kirk Metabolic side effects of antipsychotic drug treatment-pharmacological mechanisms, Pharmacol. Ther 125 2010 169 179
148. K.S. Kim, Y.R. Yoon, H.J. Lee, S. Yoon, S.-Y. Kim, S.W. Shin, J.J. An, M.-S. Kim, S.-Y. Choi, W. Sun, and J.-H. Baik Enhanced hypothalamic leptin signaling in mice lacking dopamine D2 receptors J. Biol. Chem. 285 2010 8905 8917
149. E. Tiligada, and J.F. Wilson Regulation of alpha-melanocyte-stimulating hormone release from superfused slices of rat hypothalamus by serotonin and the interaction of serotonin with the dopaminergic system inhibiting peptide release Brain Res. 503 1989 225 228
150. A. Vicentic, and D.C. Jones The CART (cocaine- and amphetamine-regulated transcript) system in appetite and drug addiction J. Pharmacol. Exp. Ther. 320 2007 499 506
151. M. Zhang, L. Han, and Y. Xu Roles of cocaine- and amphetamine-regulated transcript in the central nervous system Clin. Exp. Pharmacol. Physiol. 39 2012 586 592
152. J. Douglass, and S. Daoud Characterization of the human cDNA and genomic DNA encoding CART: a cocaine- and amphetamine-regulated transcript Gene 169 1996 241 245
153. P. Kristensen, M.E. Judge, L. Thim, U. Ribel, K.N. Christjansen, B.S. Wulff, J.T. Clausen, P.B. Jensen, O.D. Madsen, N. Vrang, P.J. Larsen, and S. Hastrup Hypothalamic CART is a new anorectic peptide regulated by leptin Nature 393 1998 72 76
154. K.T. Nakhate, D.M. Kokare, P.S. Singru, and N.K. Subhedar Central regulation of feeding behavior during social isolation of rat: evidence for the role of endogenous CART system Int. J. Obes. 35 2011 773 784
155. K.A. Simpson, N.M. Martin, and S.R. Bloom Hypothalamic regulation of food intake and clinical therapeutic applications Arq. Bras. Endocrinol. Metabol. 53 2009 120 128
156. H. Davidowa, Y. Li, and A. Plagemann The main effect of cocaine- and amphetamine-regulated transcript (CART) peptide on hypothalamic neuronal activity depends on the nutritional state of rats Neuro Endocrinol. Lett. 26 2005 29 34
157. D. Cota, J.G. Barrera, and R.J. Seeley Leptin in energy balance and reward: two faces of the same coin?[comment] Neuron 51 2006 678 680
158. V. Di Marzo, A. Ligresti, and L. Cristino The endocannabinoid system as a link between homoeostatic and hedonic pathways involved in energy balance regulation Int. J. Obes. 33 2009 S18 S24
159. F. Rohner-Jeanrenaud, L.S. Craft, J. Bridwell, T.M. Suter, F.C. Tinsley, D.L. Smiley, D.R. Burkhart, M.A. Statnick, M.L. Heiman, E. Ravussin, and J.F. Caro Chronic central infusion of cocaine- and amphetamine-regulated transcript (CART 55-102): effects on body weight homeostasis in lean and high-fat-fed obese rats Int. J. Obes. Relat. Metab. Disord. 26 2002 143 149
160. D. Sezlev, M. Ak, T. YanIk, C. Kursungoz, S. Akarsu, and L. Sutcigil The role of central neuropeptides in weight gain caused by olanzapine Eur. Psychiatry 28 2013 1
161. M.H. Donovan, and L.H. Tecott Serotonin and the regulation of mammalian energy balance Front. Neurosci. 7 2013 36
162. N.I. Chowdhury, R.P. Souza, A.K. Tiwari, E.J. Brandl, M. Sicard, H.Y. Meltzer, J.A. Lieberman, J.L. Kennedy, and D.J. Müller Investigation of melanocortin system gene variants in antipsychotic-induced weight gain World J. Biol. Psychiatry 15 2014 251 258
163. A.K. Malhotra, C.U. Correll, N.I. Chowdhury, D.J. Müller, P.K. Gregersen, A.T. Lee, A.K. Tiwari, J.M. Kane, W.W. Fleischhacker, R.S. Kahn, R.A. Ophoff, J.A. Lieberman, H.Y. Meltzer, T. Lencz, and J.L. Kennedy Association between common variants near the melanocortin 4 receptor gene and severe antipsychotic drug-Induced weight gain Arch. Gen. Psychiatry 69 2012 904 912
164. 1 receptor activation in rodents Life Sci. 63 1998 463 476
165. S. Jeck-Thole, and W. Wagner Betahistine: a retrospective synopsis of safety data Drug Saf. 29 2006 1049 1059
166. B. Tighilet, C. Mourre, S. Trottier, and M. Lacour Histaminergic ligands improve vestibular compensation in the cat: behavioural: neurochemical and molecular evidence Eur. J. Pharmacol. 568 2007 149 163
167. N. Barak Betahistine: what's new on the agenda Expert Opin. Investig. Drugs 17 2008 795 804
168. A. Szelag, and M.A. Trocha Merwid-Lad Betahistine inhibits food intake in rats Pol. J. Pharmacol. 53 2001 701 707
169. C. Deng, J. Lian, N. Pai, and X.F. Huang Reducing olanzapine-induced weight gain side effect by using betahistine: a study in the rat model J. Psychopharmacol. (Oxf.) 26 2012 1271 1279
170. J. Lieberman, T. Stroup, and M. Swartz Effectiveness of antipsychotic drugs in patients with chronic schizophrenia N. Engl. J. Med. 353 2005 1209 1223
171. N. Barak, F.L. Greenway, K. Fujioka, L.J. Aronne, and R.F. Kushner Effect of histaminergic manipulation on weight in obese adults: a randomized placebo controlled trial Int. J. Obes. 32 2008 1559 1565
172. A.H. Ali, L.B. Yanoff, E.A. Stern, A. Akomeah, A. Courville, M. Kozlosky, S.M. Brady, K.A. Calis, J.C. Reynolds, M.K. Crocker, N. Barak, and J.A. Yanovski Acute effects of betahistine hydrochloride on food intake and appetite in obese women: a randomized, placebo-controlled trial Am. J. Clin. Nutr. 92 2010 1290 1297
173. 3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients Int. Clin. Psychopharmacol. 20 2005 101 103
174. M. Poyurovsky, C. Fuchs, A. Pashinian, A. Levi, R. Weizman, and A. Weizman Reducing antipsychotic-induced weight gain in schizophrenia: a double-blind placebo-controlled study of reboxetine-betahistine combination Psychopharmacology (Berl.) 226 2013 615 622
175. M. Poyurovsky, C. Fuchs, A. Pashinian, A. Levi, S. Faragian, R. Maayan, and I. Gil-Ad Attenuating effect of reboxetine on appetite and weight gain in olanzapine-treated schizophrenia patients: a double-blind placebo-controlled study Psychopharmacology (Berl.) 192 2007 441 448
176. N. Barak, Y. Beck, Betahistine safely mitigates olanzapine induced weight gain and sleepiness, Collegium Internationale Neuro-Psychopharmacoloicum XXVII World Congress, Vol. 13, Hongkong, China, 2010, p. 87.
177. L. Maayan, The attenuation of second generation antipsychotic induced weight gain in adolescents and young adults using betahistine: a double-blind, placebo-controlled trial. http://www.clinicalconnection.com/exp/EPVS.aspx?studyID=258108&slID=1439477 (accessed 30.06.15).
178. M. He, Q. Zhang, C. Deng, H. Wang, J. Lian, and X.F. Huang Olanzapine-activated AMPK signaling in the dorsal vagal complex is attenuated by histamine H1 receptor agonistin female rats Endocrinology 155 2014 4895 4904
179. H.Y. Meltzer Illuminating the molecular basis for some antipsychotic drug-induced metabolic burden Proc. Natl. Acad. Sci. U.S.A. 104 2007 3019 3020
180. A. Stefanidis, A.N.A. Verty, A.M. Allen, N.C. Owens, M.A. Cowley, and B.J. Oldfield The role of thermogenesis in antipsychotic drug-induced weight gain Obesity 17 2008 16 24
181. M. Lopez, R. Lage, A.K. Saha, D. Perez-Tilve, M.J. Vazquez, L. Varela, S. Sangiao-Alvarellos, S. Tovar, K. Raghay, S. Rodriguez-Cuenca, R.M. Deoliveira, T. Castaneda, R. Datta, J.Z. Dong, M. Culler, M.W. Sleeman, C.V. Alvarez, R. Gallego, C.J. Lelliott, D. Carling, M.H. Tschop, C. Dieguez, and A. Vidal-Puig Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin Cell Metab. 7 2008 389 399
182. 3 receptor antagonist, powerfully suppresses peptide YY-induced food intake in rats Biol. Psychiatry 45 1999 475 481
183. 4 receptors: independent regulation of food intake and energy expenditure Peptides 27 2006 326 332
184. M. Lopez, L. Varela, M.J. Vazquez, S. Rodriguez-Cuenca, C.R. Gonzalez, V.R. Velagapudi, D.A. Morgan, E. Schoenmakers, K. Agassandian, R. Lage, P.B. Martinez de Morentin, S. Tovar, R. Nogueiras, D. Carling, C. Lelliott, R. Gallego, M. Oresic, K. Chatterjee, A.K. Saha, K. Rahmouni, C. Dieguez, and A. Vidal-Puig Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance Nat. Med. 16 2010 1001 1008
185. Shaun F. Morrison, Christopher J. Madden, and D. Tupone Central neural regulation of brown adipose tissue thermogenesis and energy expenditure Cell Metab. 19 2014 741 756
186. Z. Wan, J. Root-McCaig, L. Castellani, B.E. Kemp, G.R. Steinberg, and D.C. Wright Evidence for the role of AMPK in regulating PGC-1 alpha expression and mitochondrial proteins in mouse epididymal adipose tissue Obesity (Silver Spring) 22 2014 730 738
187. Q. Zhang, J. Lian, M. He, C. Deng, H. Wang, and X.-F. Huang Olanzapine reduced brown adipose tissue thermogenesis and locomotor activity in female rats Prog. Neuropsychopharmacol. Biol. Psychiatry. 51 2014 172 180
188. J. Horacek, V. Bubenikova-Valesova, M. Kopecek, T. Palenicek, C. Dockery, P. Mohr, and C. Hoschl Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia CNS Drugs 20 2006 389 409
189. H. Meltzer, and B. Massey The role of serotonin receptors in the action of atypical antipsychotic drugs Curr. Opin. Pharmacol. 11 2011 59 67
190. N. Bozina, V. Medved, M.R. Kuzman, I. Sain, and J. Sertic Association study of olanzapine-induced weight gain and therapeutic response with SERT gene polymorphisms in female schizophrenic patients J. Psychopharmacol. (Oxf.) 21 2007 728 734
191. J.P. Zhang, and A.K. Malhotra Pharmacogenetics and antipsychotics: therapeutic efficacy and side effects prediction Expert Opin. Drug Metab. Toxicol. 7 2011 9 37
192. 2 receptors for antipsychotic activity Handb. Exp. Pharmacol. 212 2012 27 52
193. 2(high) receptors CNS Neurosc. Ther. 17 2011 118 132
194. O.D. Howes, J. Kambeitz, E. Kim, D. Stahl, M. Slifstein, A. Abi-Dargham, and S. Kapur The nature of dopamine dysfunction in schizophrenia and what this means for treatment Arch. Gen. Psychiatry 69 2012 776 786
195. 2 receptor binding density Prog. Neuropsychopharmacol. Biol. Psychiatry. 47 2013 62 68
196. J. Lian, X.F. Huang, N. Pai, and C. Deng Chronic betahistine co-treatment reverses olanzapine's effects on dopamine D(2) but not 5-HT2A/2C bindings in rat brains Prog. Neuropsychopharmacol. Biol. Psychiatry 56 2015 75 80
197. T. Kuroki, N. Nagao, and T. Nakahara Neuropharmacology of second-generation antipsychotic drugs: a validity of the serotonin-dopamine hypothesis V.D.M. Giuseppe Di, GiovannE. Ennio, Progress in Brain Research vol. 172 2008 Elsevier 199 212
198. F.I. Tarazi, K. Zhang, and R.J. Baldessarini Long-term effects of olanzapine risperidone, and quetiapine on serotonin 1A, 2A and 2C receptors in rat forebrain regions Psychopharmacology (Berl.) 161 2002 263 270
199. 2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment Prog. Neuropsychopharmacol. Biol. Psychiatry 29 2005 1021 1028
200. F.I. Tarazi, K. Zhang, and R.J. Baldessarini 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. 297 2001 711 717
201. A.-N. Samaha, P. Seeman, J. Stewart, H. Rajabi, and S. Kapur Breakthrough dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time J. Neurosci. 27 2007 2979 2986
202. M. Lacour, and O. Sterkers Histamine and betahistine in the treatment of vertigo: elucidation of mechanisms of action CNS Drugs 15 2001 853 870
203. A. Fossati, D. Barone, and C. Benvenuti Binding affinity profile of betahistine and its metabolites for central histamine receptors of rodents Pharmacol. Res. 43 2001 389 392