Advertisement

Role of the Histamine H3 Receptor in the Central Nervous System

  • Eberhard SchlickerEmail author
  • Markus Kathmann
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 241)

Abstract

The Gi/o protein-coupled histamine H3 receptor is distributed throughout the central nervous system including areas like cerebral cortex, hippocampus and striatum with the density being highest in the posterior hypothalamus, i.e. the area in which the histaminergic cell bodies are located. In contrast to the other histamine receptor subtypes (H1, H2 and H4), the H3 receptor is located presynaptically and shows a constitutive activity. In detail, H3 receptors are involved in the inhibition of histamine release (presynaptic autoreceptor), impulse flow along the histaminergic neurones (somadendritic autoreceptor) and histamine synthesis. Moreover, they occur as inhibitory presynaptic heteroreceptors on serotoninergic, noradrenergic, dopaminergic, glutamatergic, GABAergic and perhaps cholinergic neurones. This review shows for four functions of the brain that the H3 receptor represents a brake against the wake-promoting, anticonvulsant and anorectic effect of histamine (via postsynaptic H1 receptors) and its procognitive activity (via postsynaptic H1 and H2 receptors). Indeed, H1 agonists and H3 inverse agonists elicit essentially the same effects, at least in rodents; these effects are opposite in direction to those elicited by brain-penetrating H1 receptor antagonists in humans. Although the benefit for H3 inverse agonists for the symptomatic treatment of dementias is inconclusive, several members of this group have shown a marked potential for the treatment of disorders associated with excessive daytime sleepiness. In March 2016, the European Commission granted a marketing authorisation for pitolisant (WakixR) (as the first representative of the H3 inverse agonists) for the treatment of narcolepsy.

Keywords

Epileptic seizures Food intake Histamine H3 receptor Histaminergic neurones Learning and memory Narcolepsy Noradrenergic neurones Pitolisant Presynaptic receptors Sleep-wake regulation 

References

  1. Anichtchik OV, Peitsaro N, Rinne JO, Kalimo H, Panula P (2001) Distribution and modulation of histamine H3 receptors in basal ganglia and frontal cortex of healthy controls and patients with Parkinson’s disease. Neurobiol Dis 8:707–716PubMedCrossRefGoogle Scholar
  2. Arrang JM, Garbarg M, Schwartz JC (1983) Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature 302:832–837PubMedCrossRefGoogle Scholar
  3. Arrang JM, Garbarg M, Schwartz JC (1987a) Auto-inhibition of histamine synthesis mediated by presynaptic H3-receptors. Neuroscience 23:149–157PubMedCrossRefGoogle Scholar
  4. Arrang JM, Garbarg M, Lancelot JC, Lecomte JM, Pollard H, Robba M, Schunack W, Schwartz JC (1987b) Highly potent and selective ligands for histamine H3-receptors. Nature 327:117–123PubMedCrossRefGoogle Scholar
  5. Arrang JM, Devaux B, Chodkiewicz JP, Schwartz JC (1988) H3-Receptors control histamine release in human brain. J Neurochem 51:105–108PubMedCrossRefGoogle Scholar
  6. Bhowmik M, Khanam R, Vohora D (2012) Histamine H3 receptor antagonists in relation to epilepsy and neurodegeneration: a systemic consideration of recent progress and perspectives. Br J Pharmacol 167:1398–1414PubMedPubMedCentralCrossRefGoogle Scholar
  7. Bonaventure P, Letavic M, Dugovic C, Wilson S, Aluisio L, Pudiak C, Lord B, Mazur C, Kamme F, Nishino S, Carruthers N, Lovenberg T (2007) Histamine H3 receptor antagonists: from target identification to drug leads. Biochem Pharmacol 73:1084–1096PubMedCrossRefGoogle Scholar
  8. Bongers G, Krueger KM, Miller TR, Baranowski JL, Estvander BR, Witte DG, Strakhova MI, van Meer P, Bakker RA, Cowart MD, Hancock AA, Esbenshade TA, Leurs R (2007) An 80-amino acid deletion in the third intracellular loop of a naturally occurring human histamine H3 isoform confers pharmacological differences and constitutive activity. J Pharmacol Exp Ther 323:888–898PubMedCrossRefGoogle Scholar
  9. Brown RE, Haas HL (1999) On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus. J Physiol 515:777–786PubMedPubMedCentralCrossRefGoogle Scholar
  10. Chazot PL, Hann V, Wilson C, Lees G, Thompson CL (2001) Immunological identification of the mammalian H3 histamine receptor in the mouse brain. Neuroreport 12:259–262PubMedCrossRefGoogle Scholar
  11. Chen Z, Sugimoto Y, Kamei C (1999) Effects of intracerebroventricular injection of α-fluoromethylhistidine on radial maze performance in rats. Pharmacol Biochem Behav 64:513–518PubMedCrossRefGoogle Scholar
  12. Chen Z, Li WD, Zhu LJ, Shen YJ, Wei EQ (2002) Effects of histidine, a precursor of histamine, on pentylenetetrazole-induced seizures in rats. Acta Pharmacol Sin 23:361–366PubMedGoogle Scholar
  13. Chen Z, Li Z, Sakurai E, Mobarakeh JI, Ohtsu H, Watanabe T, Watanabe T, Iinuma K, Yanai K (2003) Chemical kindling induced by pentylenetetrazol in histamine H1 receptor gene knockout mice (H1KO), histidine decarboxylase-deficient mice (HDC–/–) and mast cell-deficient W/Wv mice. Brain Res 968:162–166PubMedCrossRefGoogle Scholar
  14. Clapp RH, Luckman SM (2012) Proxyfan acts as a neutral antagonist of histamine H3 receptors in the feeding-related hypothalamic ventromedial nucleus. Br J Pharmacol 167:1099–1110PubMedPubMedCentralCrossRefGoogle Scholar
  15. Clark EA, Hill SJ (1996) Sensitivity of histamine H3 receptor agonist-stimulated [35S] GTP gamma[S] binding to pertussis toxin. Eur J Pharmacol 296:223–225PubMedCrossRefGoogle Scholar
  16. Dai H, Kaneko K, Kato H, Fujii S, Jing Y, Xu A, Sakurai E, Kato M, Okamura N, Kuramasu A, Yanai K (2007) Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors. Neurosci Res 57:306–313PubMedCrossRefGoogle Scholar
  17. Dauvilliers Y, Bassetti C, Lammers GJ, Arnulf I, Mayer G, Rodenbeck A, Lehert P, Ding CL, Lecomte JM, Schwartz JC, Harmony I study group (2013) Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial. Lancet Neurol 12:1068–1075Google Scholar
  18. De Luca R, Suvorava T, Yang D, Baumgärtel W, Kojda G, Haas HL, Sergeeva O (2016) Identification of histaminergic neurons through histamine 3 receptor-mediated autoinhibition. Neuropharmacology 106:102–115PubMedCrossRefGoogle Scholar
  19. Dere E, De Souza Silva MA, Topic B, Spieler RE, Haas HL, Huston JP (2003) Histidine-decarboxylase knockout mice show deficient nonreinforced episodic object memory, improved negatively reinforced water-maze performance, and increased neo- and ventro-striatal dopamine turnover. Learn Mem 10:510–519PubMedPubMedCentralCrossRefGoogle Scholar
  20. Dere E, Zlomuzica A, Viggiano D, Ruocco LA, Watanabe T, Sadile AG, Huston JP, De Souza Silva MA (2008) Episodic-like and procedural memory impairments in histamine H1 receptor knockout mice coincide with changes in acetylcholine esterase activity in the hippocampus and dopamine turnover in the cerebellum. Neuroscience 157:532–541PubMedCrossRefGoogle Scholar
  21. Dimitriadou V, Rouleau A, Tuong MDT, Newlands GJF, Miller HRP, Luffau G, Schwartz JC, Garbarg M (1994) Functional relationship between mast cells and C-sensitive nerve fibres evidenced by histamine H3-receptor modulation in rat lung and spleen. Clin Sci 87:151–163PubMedCrossRefGoogle Scholar
  22. Doreulee N, Yanovsky Y, Flagmeyer I, Stevens DR, Haas HL, Brown RE (2001) Histamine H3 receptors depress synaptic transmission in the corticostriatal pathway. Neuropharmacology 40:106–113PubMedCrossRefGoogle Scholar
  23. Drutel G, Peitsaro N, Karlstedt K, Wieland K, Smit MJ, Timmerman H, Panula P, Leurs R (2001) Identification of rat H3 receptor isoforms with different brain expression and signaling properties. Mol Pharmacol 59:1–8PubMedGoogle Scholar
  24. Egan M, Yaari R, Liu L, Ryan M, Peng Y, Lines C, Michelson D (2012) Pilot randomized controlled study of a histamine receptor inverse agonist in the symptomatic treatment of AD. Curr Alzheimer Res 9:481–490PubMedCrossRefGoogle Scholar
  25. Ellenbroek BA, Ghiabi B (2014) The other side of the histamine H3 receptor. Trends Neurosci 37:191–199PubMedCrossRefGoogle Scholar
  26. Ferrada C, Ferré S, Casadó V, Cortés A, Justinova Z, Barnes C, Canela EI, Goldberg SR, Leurs R, Lluis C, Franco R (2008) Interactions between histamine H3 and dopamine D2 receptors and the implications for striatal function. Neuropharmacology 55:190–197PubMedCrossRefGoogle Scholar
  27. Ferrada C, Moreno E, Casadó V, Bongers G, Cortés A, Mallol J, Canela EI, Leurs R, Ferré S, Lluís C, Franco R (2009) Marked changes in signal transduction upon heteromerization of dopamine D1 and histamine H3 receptors. Br J Pharmacol 157:64–75PubMedPubMedCentralCrossRefGoogle Scholar
  28. Feuerstein TJ (2008) Presynaptic receptors for dopamine, histamine and serotonin. Handb Exp Pharmacol 184:289–338CrossRefGoogle Scholar
  29. Garbarg M, Arrang M, Rouleau A, Ligneau X, Tuong MDT, Schwartz JC, Ganellin CR (1992) S-[2-(4-imidazolyl)ethyl]isothiourea, a highly specific and potent histamine H3 receptor agonist. J Pharmacol Exp Ther 263:304–310PubMedGoogle Scholar
  30. Gbahou F, Rouleau A, Morisset S, Parmentier R, Crochet S, Lin JS, Ligneau X, Tardivel-Lacombe J, Stark H, Schunack W, Ganellin CR, Schwartz JC, Arrang JM (2003) Protean agonism at histamine H3 receptors in vitro and in vivo. Proc Natl Acad Sci 100:11086–11091PubMedPubMedCentralCrossRefGoogle Scholar
  31. Gbahou F, Davenas E, Morisset S, Arrang JM (2010) Effects of betahistine at histamine H3 receptors: Mixed inverse agonism/agonism in vitro and partial inverse agonism in vivo. J Pharmacol Exp Ther 334:945–954PubMedCrossRefGoogle Scholar
  32. Giovannini MG, Efoudebe M, Passani MB, Baldi E, Bucherelli C, Giachi F, Corradetti R, Blandina P (2003) Improvement in fear memory by histamine-elicited ERK2 activation in hippocampal CA3 cells. J Neurosci 23:9016–9023PubMedGoogle Scholar
  33. Gondard E, Anaclet C, Akaoka H, Guo RX, Zhang M, Buda C, Franco P, Kotani H, Lin JS (2013) Enhanced histaminergic neurotransmission and sleep-wake alterations, a study in histamine H3-receptor knock-out mice. Neuropsychopharmacology 38:1015–1031PubMedPubMedCentralCrossRefGoogle Scholar
  34. Grove RA, Harrington CM, Mahler A, Beresford I, Maruff P, Lowy MT, Nicholls AP, Boardley RL, Berges AC, Nathan PJ, Horrigan JP (2014) A randomized, double-blind, placebo-controlled, 16-week study of the H3 receptor antagonist, GSK239512 as a monotherapy in subjects with mild-to-moderate Alzheimer’s disease. Curr Alzheimer Res 11:47–58PubMedCrossRefGoogle Scholar
  35. Haas HL, Sergeeva OA, Selbach O (2008) Histamine in the nervous system. Physiol Rev 88:1183–1241PubMedCrossRefGoogle Scholar
  36. Haig GM, Pritchett Y, Meier A, Othman AA, Hall C, Gault LM, Lenz RA (2014) A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer’s dementia. J Alzheimers Dis 42:959–971PubMedGoogle Scholar
  37. Hancock AA, Esbenshade TA, Krueger KM, Yao BB (2003) Genetic and pharmacological aspects of histamine H3 receptor heterogeneity. Life Sci 73:3043–3072PubMedCrossRefGoogle Scholar
  38. Hirai T, Okuma C, Harada C, Mio M, Ohtsu H, Watanabe T, Kamei C (2004) Development of amygdaloid kindling in histidine decarboxylase-deficient and histamine H1 receptor-deficient mice. Epilepsia 45:309–313PubMedCrossRefGoogle Scholar
  39. Hough LB (1988) Cellular localization and possible functions for brain histamine: recent progress. Prog Neurobiol 30:469–505PubMedCrossRefGoogle Scholar
  40. Howlett AC (2005) Cannabinoid receptor signaling. Handb Exp Pharmacol 168:53–79CrossRefGoogle Scholar
  41. Iinuma K, Yokoyama H, Otsuki T, Yanai K, Watanabe T, Ido T, Itoh M (1993) Histamine H1 receptors in complex partial seizures. Lancet 341:238PubMedCrossRefGoogle Scholar
  42. Jansen FP, WU TS, Voss HP, Steinbusch HWM, Vollinga RC, Rademaker B, Bast A, Timmerman H (1994) Characterization of the binding of the first selective radiolabelled histamine H3-receptor antagonist, [125I]iodophenpropit, to rat brain. Brit J Pharmacol 113:355–362Google Scholar
  43. Jin CY, Panula P (2005) The laminar histamine receptor system in human prefrontal cortex suggests multiple levels of histaminergic regulation. Neuroscience 132:137–149PubMedCrossRefGoogle Scholar
  44. Jin CY, Kalimo H, Panula P (2002) The histaminergic system in human thalamus: correlation of innervation to receptor expression. Eur J Neurosci 15:1125–1138PubMedCrossRefGoogle Scholar
  45. Jin CL, Zhuge ZB, Wu DC, Zhu YY, Wang S, Luo JH, Chen Z (2007) Lesion of the tuberomammillary nucleus E2-region attenuates postictal seizure protection in rats. Epilepsy Res 73:250–258PubMedCrossRefGoogle Scholar
  46. Jones BE (2005) From waking to sleeping: neuronal and chemical substrates. Trends Pharmacol Sci 26:578–586PubMedCrossRefGoogle Scholar
  47. Jørgensen EA, Knigge U, Watanabe T, Warberg J, Kjaer A (2005) Histaminergic neurons are involved in the orexigenic effect of orexin-A. Neuroendocrinology 82:70–77PubMedCrossRefGoogle Scholar
  48. Kubista H, Boehm S (2006) Molecular mechanisms underlying the modulation of exocytotic noradrenaline release via presynaptic receptors. Pharmacol Ther 112:213–242PubMedCrossRefGoogle Scholar
  49. Kukko-Lukjanov TK, Lintunen M, Jalava N, Lauren HB, Lopez-Picon FR, Michelsen KA, Panula P, Holopainen IE (2010) Involvement of histamine 1 receptor in seizure susceptibility and neuroprotection in immature mice. Epilepsy Res 90:8–15PubMedCrossRefGoogle Scholar
  50. Kukko-Lukjanov TK, Gronman M, Lintunen M, Lauren HB, Michelsen KA, Panula P, Holopainen IE (2012) Histamine 1 receptor knock out mice show age-dependent susceptibility to status epilepticus and consequent neuronal damage. Epilepsy Res 100:80–92PubMedCrossRefGoogle Scholar
  51. Lamberty Y, Margineanu DG, Dassesse D, Klitgaard H (2003) H3 agonist immepip markedly reduces cortical histamine release, but only weakly promotes sleep in the rat. Pharmacol Res 48:193–198PubMedCrossRefGoogle Scholar
  52. Łażewska D, Kieć-Kononowicz K (2014) New developments around histamine H3 receptor antagonists/inverse agonists: a patent review (2010 - present). Expert Opin Ther Pat 24:89–111PubMedCrossRefGoogle Scholar
  53. Lecklin A, Tuomisto L (1998) The blockade of H1 receptors attenuates the suppression of feeding and diuresis induced by inhibition of catabolism. Pharmacol Biochem Behav 59:753–758PubMedCrossRefGoogle Scholar
  54. Leurs R, Bakker RA, Timmerman H, de Esch IJP (2005) The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov 4:107–120PubMedCrossRefGoogle Scholar
  55. Leu-Semenescu S, Nittur N, Golmard JL, Arnulf I (2014) Effects of pitolisant, a histamine H3 inverse agonist, in drug-resistant idiopathic and symptomatic hypersomnia: a chart review. Sleep Med 15:681–687PubMedCrossRefGoogle Scholar
  56. Liblau RS, Vassalli A, Seifinejad A, Tafti M (2015) Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy. Lancet Neurol 14:318–328PubMedCrossRefGoogle Scholar
  57. Liedtke S, Flau K, Kathmann M, Schlicker E, Stark H, Meier G, Schunack W (2003) Replacement of imidazole by a piperidine moiety differentially affects the potency of histamine H3-receptor antagonists. Naunyn Schmiedebergs Arch Pharmacol 367:43–50PubMedCrossRefGoogle Scholar
  58. Ligneau X, Garbarg M, Vizuete ML, Diaz J, Purand K, Stark H, Schunack W, Schwartz JC (1994) [125I]Iodoproxyfan, a new antagonist to label and visualize cerebral histamine H3 receptors. J Pharmacol Exp Ther 271:452–459PubMedGoogle Scholar
  59. Ligneau X, Morisset S, Tardivel-Lacombe J, Gbahou F, Ganellin CR, Stark H, Schunack W, Schwartz JC, Arrang JM (2000) Distinct pharmacology of rat and human histamine H3 receptors: role of two amino acids in the third transmembrane domain. Br J Pharmacol 131:1247–1250PubMedPubMedCentralCrossRefGoogle Scholar
  60. Lin JS (2000) Brain structures and mechanisms involved in the control of cortical activation and wakefulness, with emphasis on the posterior hypothalamus and histaminergic neurons. Sleep Med Rev 4:471–503PubMedCrossRefGoogle Scholar
  61. Lin JS, Sakai K, Vanni-Mercier G, Arrang JM, Garbarg M, Schwartz JC, Jouvet M (1990) Involvement of histaminergic neurons in arousal mechanisms demonstrated with H3-receptor ligands in the cat. Brain Res 523:325–330PubMedCrossRefGoogle Scholar
  62. Lin JS, Dauvilliers Y, Arnulf I, Bastuji H, Anaclet C, Parmentier R, Kocher L, Yanagisawa M, Lehert P, Ligneau X, Perrin D, Robert P, Roux M, Lecomte JM, Schwartz JC (2008) An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: studies in orexin–/– mice and patients. Neurobiol Dis 30:74–83PubMedCrossRefGoogle Scholar
  63. Lin JS, Sergeeva OA, Haas HL (2011) Histamine H3 receptors and sleep-wake regulation. J Pharmacol Exp Ther 336:17–23PubMedCrossRefGoogle Scholar
  64. Lippert U, Artuc M, Grützkau A, Babina M, Guhl S, Haase I, Blaschke V, Zachmann K, Knosalla M, Middel P, Krüger-Krasagakis S, Henz BM (2004) Human skin mast cells express H2 and H4, but not H3 receptors. J Invest Dermatol 123:116–123PubMedCrossRefGoogle Scholar
  65. Lovenberg TW, Roland BL, Wilson SJ, Jiang X, Pyati J, Huvar A, Jackson MR, Erlander MG (1999) Cloning and functional expression of the human histamine H3 receptor. Mol Pharmacol 55:1101–1107PubMedGoogle Scholar
  66. Lundius EG, Sanchez-Alavez M, Ghochani Y, Klaus J, Tabarean IV (2010) Histamine influences body temperature by acting at H1 and H3 receptors on distinct populations of preoptic neurons. J Neurosci 30:4369–4381PubMedPubMedCentralCrossRefGoogle Scholar
  67. Malmberg-Aiello P, Ipponi A, Bartolini A, Schunack W (2000) Antiamnesic effect of metoprine and of selective histamine H1 receptor agonists in a modified mouse passive avoidance test. Neurosci Lett 288:1–4PubMedCrossRefGoogle Scholar
  68. Malmlöf K, Hastrup S, Wulff BS, Hansen BC, Peschke B, Jeppesen CB, Hohlweg R, Rimvall K (2007) Antagonistic targeting of the histamine H3 receptor decreases caloric intake in higher mammalian species. Biochem Pharmacol 73:1237–1242PubMedCrossRefGoogle Scholar
  69. Masaki T, Chiba S, Yasuda T, Noguchi H, Kakuma T, Watanabe T, Sakata T, Yoshimatsu H (2004) Involvement of hypothalamic H1 receptor in the regulation of feeding rhythm and obesity. Diabetes 53:2250–2260PubMedCrossRefGoogle Scholar
  70. McLeod RL, Aslanian R, Del Prado M, Duffy R, Egan RW, Kreutner W, McQuade R, Hey JA (1998) Sch 50971, an orally active histamine H3 receptor agonist, inhibits central neurogenic vascular inflammation and produces sedation in the guinea pig. J Pharmacol Exp Ther 287:43–50PubMedGoogle Scholar
  71. Meier G, Apelt J, Reichert U, Grassmann S, Ligneau X, Elz S, Leurquin F, Ganellin CR, Schwartz JC, Schunack W, Stark H (2001) Influence of imidazole replacement in different structural classes of histamine H3-receptor antagonists. Eur J Pharm Sci 13:249–259PubMedCrossRefGoogle Scholar
  72. Miyazaki S, Imaizumi M, Onodera K (1995a) Effects of thioperamide on the cholinergic system and the step-through passive avoidance test in mice. Methods Find Exp Clin Pharmacol 17:653–658PubMedGoogle Scholar
  73. Miyazaki S, Imaizumi M, Onodera K (1995b) Effects of thioperamide, a histamine H3-receptor antagonist, on a scopolamine-induced learning deficit using an elevated plus-maze test in mice. Life Sci 57:2137–2144PubMedCrossRefGoogle Scholar
  74. Monti JM, Orellana C, Boussard M, Jantos H, Olivera S (1990) Sleep variables are unaltered by zolantidine in rats: are histamine H2-receptors not involved in sleep regulation? Brain Res Bull 25:229–231PubMedCrossRefGoogle Scholar
  75. Monti JM, Jantos H, Boussard M, Altier H, Orellana C, Olivera S (1991) Effects of selective activation or blockade of the histamine H3 receptor on sleep and wakefulness. Eur J Pharmacol 205:283–287PubMedCrossRefGoogle Scholar
  76. Nakazi M, Bauer U, Nickel T, Kathmann M, Schlicker E (2000) Inhibition of serotonin release in the mouse brain via presynaptic cannabinoid CB1 receptors. Naunyn Schmiedebergs Arch Pharmacol 361:19–24PubMedCrossRefGoogle Scholar
  77. Nathan PJ, Boardley R, Scott N, Berges A, Maruff P, Sivananthan T, Upton N, Lowy MT, Nestor PJ, Lai R (2013) The safety, tolerability, pharmacokinetics and cognitive effects of GSK239512, a selective histamine H3 receptor antagonist in patients with mild to moderate Alzheimer’s disease: a preliminary investigation. Curr Alzheimer Res 10:240–251PubMedCrossRefGoogle Scholar
  78. Nickel T, Bauer U, Schlicker E, Kathmann M, Göthert M, Sasse A, Stark H, Schunack W (2001) Novel histamine H3-receptor antagonists and partial agonists with a non-aminergic structure. Br J Pharmacol 132:1665–1672PubMedPubMedCentralCrossRefGoogle Scholar
  79. Nishino S, Okura M, Mignot E (2000) Narcolepsy: genetic predisposition and neuropharmacological mechanisms. Sleep Med Rev 4:57–99PubMedCrossRefGoogle Scholar
  80. Ookuma K, Sakata T, Fukagawa K, Yoshimatsu H, Kurokawa M, Machidori H, Fujimoto K (1993) Neuronal histamine in the hypothalamus suppresses food intake in rats. Brain Res 628:235–242PubMedCrossRefGoogle Scholar
  81. Panula P, Nuutinen S (2013) The histaminergic network in the brain: basic organization and role in disease. Nat Rev Neurosci 14:472–487PubMedCrossRefGoogle Scholar
  82. Panula P, Chazot PL, Cowart M, Gutzmer R, Leurs R, Liu WLS, Stark H, Thurmond RL, Haas HL (2015) Internation Union of basic and clinical pharmacology. XCVIII. Histamine receptors. Pharmacol Rev 67:601–655PubMedPubMedCentralCrossRefGoogle Scholar
  83. Parmentier R, Ohtsu H, Djebarra-Hannas Z, Valatx JL, Watanabe T, Lin JS (2002) Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control. J Neurosci 22:7695–7711PubMedGoogle Scholar
  84. Parmentier R, Anaclet C, Guhennec C, Brousseau E, Bricout D, Giboulot T, Bozyczko-Coyne D, Spiegel K, Ohtsu H, Williams M, Lin JS (2007) The brain H3-receptor as a novel therapeutic target for vigilance and sleep-wake disorders. Biochem Pharmacol 73:1157–1171PubMedCrossRefGoogle Scholar
  85. Passani MB, Blandina P, Torrealba F (2011) The histamine H3 receptor and eating behavior. J Pharmacol Exp Ther 336:24–29PubMedCrossRefGoogle Scholar
  86. Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates, compact, 3rd edn. Academic, San DiegoGoogle Scholar
  87. Pillot C, Heron A, Cochois V, Tardivel-Lacombe J, Ligneau X, Schwartz JC, Arrang JM (2002) A detailed mapping of the histamine H3 receptor and its gene transcripts in rat brain. Neuroscience 114:173–193PubMedCrossRefGoogle Scholar
  88. Pollard H, Schwartz JC (1987) Histamine neuronal pathways and their functions. Trends Neurosci 10:86–89CrossRefGoogle Scholar
  89. Pollard H, Moreau J, Arrang JM, Schwartz JC (1993) A detailed autoradiographic mapping of histamine H3 receptors in rat brain areas. Neuroscience 52:169–189PubMedCrossRefGoogle Scholar
  90. Poyurovsky M, Fuchs C, Pashinian A, Levi A, Weizman R, Weizman A (2013) Reducing antipsychotic-induced weight gain in schizophrenia: a double-blind placebo-controlled study of reboxetine-betahistine combination. Psychopharmacol (Berl) 216:615–622CrossRefGoogle Scholar
  91. Provensi G, Blandina P, Passani MB (2016) The histaminergic system as a target for the prevention of obesity and metabolic syndrome. Neuropharmacology 106:3–12PubMedCrossRefGoogle Scholar
  92. Rahmani RH, Ingram CD (2007) Histamine controls food intake in sheep via H1 receptors. Small Ruminant Res 70:110–115CrossRefGoogle Scholar
  93. Rouleau A, Ligneau X, Tardivel-Lacombe J, Morisset S, Gbahou F, Schwartz JC, Arrang JM (2002) Histamine H3-receptor-mediated [35S]GTPγS binding: evidence for constitutive activity of the recombinant and native rat and human H3 receptors. Br J Pharmacol 135:383–392PubMedPubMedCentralCrossRefGoogle Scholar
  94. Sadek B, Stark H (2016) Cherry-picked ligands at histamine receptor subtypes. Neuropharmacology 106:56–73PubMedCrossRefGoogle Scholar
  95. Sadek B, Saad A, Subramanian D, Shafiullah M, Łażewska D, Kieć-Kononowicz K (2016) Anticonvulsant and procognitive properties of the non-imidazole histamine H3 receptor antagonist DL77 in male adult rats. Neuropharmacology 106:46–55PubMedCrossRefGoogle Scholar
  96. Sánchez-Lemus E, Arias-Montaño JA (2004) Histamine H3 receptor activation inhibits dopamine D1 receptor-induced cAMP accumulation in rat striatal slices. Neurosci Lett 364:179–184PubMedCrossRefGoogle Scholar
  97. Schlicker E, Kathmann M (2001) Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci 22:565–572PubMedCrossRefGoogle Scholar
  98. Schlicker E, Betz R, Göthert M (1988) Histamine H3 receptor-mediated inhibition of serotonin release in the rat brain cortex. Naunyn Schmiedebergs Arch Pharmacol 337:588–590PubMedCrossRefGoogle Scholar
  99. Schlicker E, Fink K, Hinterthaner M, Göthert M (1989) Inhibition of noradrenaline release in the rat brain cortex via presynaptic H3 receptors. Naunyn Schmiedebergs Arch Pharmacol 340:633–638PubMedCrossRefGoogle Scholar
  100. Schlicker E, Fink K, Detzner M, Göthert M (1993) Histamine inhibits dopamine release in the mouse striatum via presynaptic H3 receptors. J Neural Transm Gen Sect 93:1–10PubMedCrossRefGoogle Scholar
  101. Schlicker E, Werthwein S, Zentner J (1999) Histamine H3 receptor-mediated inhibition of noradrenaline release in the human brain. Fundam Clin Pharmacol 13:120–122PubMedCrossRefGoogle Scholar
  102. Schneider EH, Neumann D, Seifert R (2014a) Modulation of behavior by the histaminergic system: Lessons from H1R- and H2R-deficient mice. Neurosci Biobehav Rev 42:252–286PubMedCrossRefGoogle Scholar
  103. Schneider EH, Neumann D, Seifert R (2014b) Modulation of behavior by the histaminergic system: Lessons from HDC-, H3R- and H4R-deficient mice. Neurosci Biobehav Rev 47:101–121PubMedCrossRefGoogle Scholar
  104. Schwartz JC (2011) The histamine H3 receptor: from discovery to clinical trials with pitolisant. Br J Pharmacol 163:713–721PubMedPubMedCentralCrossRefGoogle Scholar
  105. Seifert R, Strasser A, Schneider EH, Neumann D, Dove S, Buschauer A (2013) Molecular and cellular analysis of human histamine receptor subtypes. Trends Pharmacol Sci 34:33–58PubMedCrossRefGoogle Scholar
  106. Selivanova SV, Honer M, Combe F, Isensee K, Stark H, Krämer S, Schubiger PA, Ametamey SM (2012) Radioflurinated histamine H3 receptor antagonist as a potential probe for in vivo PET imaging: radiosynthesis and pharmacological evaluation. Bioorg Med Chem 20:2889–2896PubMedCrossRefGoogle Scholar
  107. Simons FER (2004) Advances in H1-antihistamines. N Engl J Med 351:2203–2217PubMedCrossRefGoogle Scholar
  108. Slater JW, Zechnich AD, Haxby DG (1999) Second-generation antihistamines. A comparative review. Drugs 57:31–47PubMedCrossRefGoogle Scholar
  109. Stevens DR, Eriksson KS, Brown RE, Haas HL (2001) The mechanism of spontaneous firing in histamine neurons. Behav Brain Res 124:105–112PubMedCrossRefGoogle Scholar
  110. Strange PG (2010) Use of the GTPγS ([35S]GTPγS and EuGTPγS) binding assay for analysis of ligand potency and efficacy at G protein-coupled receptors. Br J Pharmacol 161:1238–1249PubMedPubMedCentralCrossRefGoogle Scholar
  111. Sturman G, Freeman P, Meade HM, Seeley NA (1994) Modulation of the intracellular and H3-histamine receptors and chemically-induced seizures in mice. Agents Actions 41:C68–C69PubMedCrossRefGoogle Scholar
  112. Szabo B, Schlicker E (2005) Effects of cannabinoids on neurotransmission. Handb Exp Pharmacol 168:327–365CrossRefGoogle Scholar
  113. Tabarean IV (2016) Histamine receptor signaling in energy homeostasis. Neuropharmacology 106:13–19PubMedCrossRefGoogle Scholar
  114. Toyota H, Dugovic C, Koehl M, Laposky AD, Weber C, Ngo K, Wu Y, Lee DH, Yanai K, Sakurai E, Watanabe T, Liu C, Chen J, Barbier AJ, Turek FW, Fung-Leung WP, Lovenberg TW (2002) Behavioral characterization of mice lacking histamine H3 receptors. Mol Pharmacol 62:389–397PubMedCrossRefGoogle Scholar
  115. Tozer MJ, Kalindjian SB (2000) Histamine H3 receptor antagonists. Exp Opin Ther Pat 10:1045–1055CrossRefGoogle Scholar
  116. Tuomisto L, Tacke U (1986) Is histamine an anticonvulsive inhibitory transmitter? Neuropharmacology 25:955–958PubMedCrossRefGoogle Scholar
  117. Uguen M, Perrin D, Belliard S, Ligneau X, Beardsley PM, Lecomte JC (2013) Preclinical evaluation of the abuse potential of pitolisant, a histamine H3 receptor inverse agonist/antagonist compared with Modafinil. Br J Pharmacol 169:632–644PubMedPubMedCentralCrossRefGoogle Scholar
  118. von Einsiedel RW, Roesch-Ely D, Diebold K, Sartor K, Mundt C, Bergemann N (2002) H2-histamine antagonist (famotidine) induced adverse CNS reactions with long-standing secondary mania and epileptic seizures. Pharmacopsychiatry 35:152–154CrossRefGoogle Scholar
  119. Weisler RH, Pandina GJ, Daly EJ, Cooper K, Gassmann-Mayer C, 31001074-ATT2001 Study Investigators (2012) Randomized clinical study of a histamine H3 receptor antagonist for the treatment of adults with attention-deficit hyperactivity disorder. CNS Drugs 26:421–434Google Scholar
  120. Wright T (2016) Menière’s disease. BMI Clin Evid 2016:pii: 0505Google Scholar
  121. Yanai K, Ryu JH, Sakai N, Takahashi T, Iwata R, Ido T, Murakami K, Watanabe T (1994) Binding characteristics of a histamine H3-receptor antagonist, [3H]S-methylthioperamide: comparison with [3H]-methylhistamine binding to rat tissues. Jpn J Pharmacol 65:107–112PubMedCrossRefGoogle Scholar
  122. Yawata I, Tanaka K, Nakagawa Y, Watanabe Y, Murashima YL, Nakano K (2004) Role of histaminergic neurons in development of epileptic seizures in EL mice. Brain Res Mol Brain Res 132:13–17PubMedCrossRefGoogle Scholar
  123. Yokoyama H (2001) The role of central histaminergic neuron system as an anticonvulsive mechanism in developing brain. Brain Dev 23:542–547PubMedCrossRefGoogle Scholar
  124. Yoshimoto R, Miyamoto Y, Shimamura K, Ishihara A, Takahashi K, Kotani H, Chen AS, Chen HY, Macneil DJ, Kanatani A, Tokita S (2006) Therapeutic potential of histamine H3 receptor agonist for the treatment of obesity and diabetes. Proc Natl Acad Sci 103:13866–13871PubMedPubMedCentralCrossRefGoogle Scholar
  125. Zlomuzica A, Viggiano D, De Souza Silva MA, Ishizuka T, Girone Carnevale UA, Ruocco LA, Watanabe T, Sadile AG, Huston JP, Dere E (2008) The histamine H1-receptor mediates the motivational effects of novelty. Eur J Neurosci 27:1461–1474PubMedCrossRefGoogle Scholar
  126. Zlomuzica A, Ruocco LA, Sadile AG, Huston JP, Dere E (2009) Histamine H1 receptor knockout mice exhibit impaired spatial memory in the eight-arm radial maze. Br J Pharmacol 157:86–91PubMedPubMedCentralCrossRefGoogle Scholar
  127. Zlomuzica A, Dere D, Dere E (2013) The histamine H1 receptor and recollection-based discrimination in a temporal order memory task in the mouse. Pharmacol Biochem Behav 111:58–63PubMedCrossRefGoogle Scholar
  128. Zlomuzica A, Dere D, Binder S, De Souza Silva MA, Huston JP, Dere E (2016) Neuronal histamine and cognitive symptoms in Alzheimer’s disease. Neuropharmacology 106:135–145PubMedCrossRefGoogle Scholar

Copyright information

© SpringerInternationalPublishingSwitzerland 2016

Authors and Affiliations

  1. 1.Institut für Pharmakologie und ToxikologieRheinische Friedrich-Wilhelms-Universität BonnBonnGermany

Personalised recommendations