nach oben

CNS Drugs

Erschienen in:

01.11.2001 | Review Article

Histamine and Betahistine in the Treatment of Vertigo

Elucidation of Mechanisms of Action

verfasst von: Dr Michel Lacour, Olivier Sterkers

Erschienen in: CNS Drugs | Ausgabe 11/2001

Einloggen, um Zugang zu erhalten

Abstract

The aim of this review is to provide clinicians with a picture of the mechanisms by which: (i) histamine and histaminergic agonists act on the vestibular system both peripherally and centrally; and (ii) histaminergic agonists and antagonists interfere with the recovery process after peripheral vestibular lesion. We have focused on betahistine, a structural analogue of histamine with weak histamine H₁ receptor agonist and more potent H₃ receptor antagonist properties, to review the currently available data on the role of the histaminergic system in the recovery process after peripheral vestibular deficits and the effects of histamine analogues in the clinical treatment of vertigo.

This review provides new insights into the basic mechanisms by which betahistine improves vestibular compensation in animal models of unilateral vestibular dysfunction, and elucidates particularly the mechanisms of action of this substance at the level of the CNS.

It is proposed that betahistine may reduce peripherally the asymmetric functioning of the sensory vestibular organs in addition to increasing vestibulocochlear blood flow by antagonising local H₃ heteroreceptors. Betahistine acts centrally by enhancing histamine synthesis within tuberomammillary nuclei of the posterior hypothalamus and histamine release within vestibular nuclei through antagonism of H₃ autoreceptors. This mechanism, together with less specific effects of betahistine on alertness regulation through cerebral H₁ receptors, should promote and facilitate central vestibular compensation.

Elucidation of the mechanisms of action of betahistine is of particular interest for the treatment of vestibular and cochlear disorders and vertigo.

Schwartz JC. Histaminergic mechanisms in brain. Annu Rev Pharmacol Toxicol 1997; 17: 325–39CrossRef

Schwartz JC. Histamine as a transmitter in brain. Life Sci 1975; 17: 503–18PubMedCrossRef

Schwartz JC, Pollard H, Quach TT. Histamine as a neurotransmitter in mammalian brain: neurochemical evidence. J Neurochem 1980; 35: 26–33PubMedCrossRef

Pollard H, Schwartz JC. Histamine neuronal pathways and their function. Trends Neurosci 1987; 10: 86–9CrossRef

Prell GD, Green JP. Histamine as a neuroregulator. Annu Rev Neurosci 1986; 9: 209–54PubMedCrossRef

Lacour M. Histamine, vestibular function and vestibular compensation. Paris: Elsevier Paris, 1998: 55

Rascol O, Hain TC, Brefel C, et al. Antivertigo medications and drug-induced vertigo. Drugs 1995; 50: 777–91PubMedCrossRef

McCabe BF, Sekitani T, Ryu JH. Drug effects on postlabyrinthectomy nystagmus. Arch Otolaryngol 1973; 98: 310–3PubMedCrossRef

Ryu JH, McCabe BF. Effects of diazepam and dimenhydrinate on the resting activity of the vestibular neuron. Aerosp Med 1974; 45: 1177–9PubMed

10.

Fischer AJE. Histamine in the treatment of vertigo. Acta Otolaryngol 1991; 479: 24–8CrossRef

11.

Wilson VJ, Melvil Jones G. Mammalian vestibular physiology. New York: Plenum Press, 1979

12.

Spoendlin HH. The ultrastructure of the vestibular sense organ. In: Wolfson RJ, editor. The vestibular system and its diseases. Philadelphia (PA): University of Pennsylvania Press, 1966: 39–68

13.

Wersäl J, Bagger-Söjbäck D. Morphology of the vestibular sense organ. In: Kornhuber H, editor. Handbook of sensory physiology, vestibular system. Vol. VI/ 1. New York: Springer-Verlag 1974: 123–70

14.

Fernandez C, Goldberg JM, Abend WK. Response to static tilts of peripheral neurons innervating otolith organs of the squirrel monkey. J Neurophysiol 1972; 35: 978–97PubMed

15.

Goldberg JM, Fernandez C. Responses of peripheral vestibular neurons to angular and linear acceleration in the squirrel monkey. Acta Otolaryngol 1975; 80: 101–10PubMedCrossRef

16.

Fernandez C, Goldberg JM. Physiology of peripheral neurons innervating otolith organs of the squirrel monkey. III: Response dynamics. J Neurophysiol 1976; 39: 996–1008PubMed

17.

Berthoz A. How does the cerebral cortex process and utilize vestibular signals? In: Balow RW, Halmagyi GM, editors. Disorders of the vestibular system. New York: Oxford University Press, 1996: 113–25

18.

Fukushima K. Corticovestibular interactions: anatomy, electrophysiology, and functional considerations. Exp Brain Res 1997; 117: 1–16PubMedCrossRef

19.

Lacour M, Borel L. Vestibular control of posture and gait. Arch Ital Biol 1993; 131: 81–104PubMed

20.

Dieringer N. Vestibular compensation: neural plasticity and its relations to functional recovery after labyrinthine lesions in frogs and other vertebrates. Prog Neurobiol 1995; 46: 97–129PubMed

21.

Brandt TH, Dieterich M. How do vestibular disorders affect spatial orientation and motion perception? In: Baloh RW, Halmagyi GM, editors. Disorders of the vestibular system. Oxford: Oxford University Press, 1996: 126–39

22.

Lacour M, Toupet M, Denise P, et al. Vestibular compensation. Facts, theories and clinical perspectives. Paris: Elsevier, 1989: 308

23.

Smith PH, Curthoys IS. Mechanisms of recovery following unilateral labyrinthectomy: a review. Brain Res Brain Res Rev 1989; 14: 155–80PubMedCrossRef

24.

Smith PH, Darlington CL. Neurochemical mechanisms of recovery from peripheral vestibular lesions (vestibular compensation). Brain Res Brain Res Rev 1991; 16: 117–3PubMedCrossRef

25.

Peppard SB. Effect of drug therapy on compensation from vestibular injury. Laryngoscope 1986; 96: 878–98PubMedCrossRef

26.

Brandt TH. Vertigo: its multisensory syndromes. London: Springer-Verlag, 1991: 1–24

27.

Halmagyi GM. Vertigo and vestibular disorders. In: Eadie J, editor. Drug therapy in neurology. Edinburgh: Churchill Livingstone, 1992: 182–195

28.

Schwartz JC. Histamine receptors in brain. Life Sci 1979; 25: 895–912PubMedCrossRef

29.

Schwartz JC, Lampart C, Rose C. Properties and regional distribution of histidine decarboxylase in rat brain. J Neurochem 1970; 17: 1527–34PubMedCrossRef

30.

Bouthenet ML, Ruat M, Sales N, et al. A detailed mapping of histamine H1 receptors in guinea-pigs central nervous system established by autoradiography with (1125) idobolpyramine. Neuroscience 1988; 26: 553–600PubMedCrossRef

31.

Arrang JM. Auto-inhibition of brain histamine release mediated by anovel class (H3) of histamine receptor. Nature 1983; 302(5911): 832–7PubMedCrossRef

32.

Schwartz JC, Arrang JM, Garbag M, et al. A third histamine receptor subtype: characterisation, localisation and functions of the H3-receptor. Agents Actions 1990; 30: 13–23PubMedCrossRef

33.

Lin JS. Système histaminergique central et états de vigilance chez le chat [thesis]. Lyon: Thèse Doct Sciences, Université Claude Bernard Lyon I, 1994

34.

Tighilet B, Lacour M. Distribution of histamine axonal fibres in the vestibular nuclei of the cat. Neuroreport 1996; 7: 873–8PubMedCrossRef

35.

Hill SJ. Distribution, properties, and functional characteristics of three classes of histamine receptors. Pharmacol Rev 1990; 42: 45–83PubMed

36.

Arrang JM, Garbarg M, Schwartz JC. H3-receptors and control of histamine release. In: Schwartz JC. Haas HL, editors. The histamine receptors. New York: Wiley-Liss, 1992: 145–60

37.

Serafin M, Khateb A, Vibert N, et al. Medial vestibular nucleus in the guinea-pig: histaminergic receptors. I. An in vitro study. Exp Brain Res 1993; 93: 242–8PubMedCrossRef

38.

Yabe T, De Waele C, Serafin M, et al. Medial vestibular nucleus in the guinea-pig: histaminergic receptors. II. An in vivo study. Exp Brain Res 1993; 93: 249–58PubMedCrossRef

39.

Takeda N, Morita M, Kubo T, et al. Histaminergic projection from the posterior hypothalamus to the medial vestibular nucleus of rats and its relation to motion sickness. In: Graham MD, Kemink JL, editors. The vestibular system: neurophysiologic and clinical research. New York: Raven Press, 1987: 571–80

40.

Jaju BP, Wang SC. Effects of diphenhydramine and dimenhydrinate on vestibular neuronal activity of cat: a search for the locus of their antimotion sickness action. J Pharmacol Exp Ther 1971; 176: 718–24PubMed

41.

Kirsten EB, Sharma JN. Microiontophoresis of acetylcholine, histamine and their antagonists on neurons in the medial and lateral vestibular nuclei of the cat. Neuropharmacology 1976; 15: 743–53PubMedCrossRef

42.

Phelan KD, Nakamura J, Gallagher JP. Histamine depolarizes rat medial vestibular nucleus neurons recorded intracellularly in vitro. Neurosci Lett 1990; 109: 287–92PubMedCrossRef

43.

Inverarity DJ, Johnston AR, McQueen DS, et al. Effects of histamine on rat medial vestibular nucleus neurones in vitro. J Physiol (Lond) 1993; 459: 466

44.

Wang JJ, Dutia MB. Effects of histamine and betahistine on rat medial vestibular nucleus neurones: possible mechanism of action of anti-histaminergic drugs in vertigo and motion sickness. Exp Brain Res 1995; 105: 18–24PubMedCrossRef

45.

Horii A, Tadeka N, Matsunaga T, et al. Effect of unilateral vestibular stimulation on histamine release from the hypothalamus of rats in vivo. Neurophysiology 1993; 90: 1822–6

46.

Gustave dit Duflo S, Gestreau C, Lacour M. Fos expression in the rat brain after exposure to gravito-inertial force changes. Brain Res 2000; 861: 333–44PubMedCrossRef

47.

Gustave dit Duflo S, Gestreau C, Tighilet B, et al. Fos expression in the cat brainstem after unilateral vestibular neurectomy. Brain Res 1999; 824: 1–17PubMedCrossRef

48.

Arrang JM, Garbarg M, Quach TT, et al. Actions of betahistine at histamine receptors in the brain. Eur J Pharmacol 1985; 111: 73–84PubMedCrossRef

49.

Laurikainen EA, Miller JM, Quirk WS, et al. Betahistine-induced vascular effects in the rat cochlear. Am J Otol 1993; 14: 24–30PubMedCrossRef

50.

Laurikainen EA, Miller JM, Nuttall AL, et al. The vascular mechanism of action of betahistine in the inner ear of the guinea pig. Eur Arch Otorhinolaryngol 1998; 255: 119–23PubMedCrossRef

51.

Hill SJ, Emson PC, Young JM. The binding of [³H] mepyramine to histamine H1 receptors in guinea-pig brain. J Neurochem 1978; 31: 997–1004PubMedCrossRef

52.

Young RC, Ganellin CR, Griffith R, et al. An approach to the design of brain-penetrating histaminergic agonists. Eur J Med Chem 1993; 28: 201–11CrossRef

53.

Suga F, Snow JB. Cochlear blood flow in response to vasodilating drugs and some related agents. Laryngoscope 1969; 79: 1956–78PubMedCrossRef

54.

Martinez DM. The effect of Serc (betahistine hydrochloride) on the circulation of the inner ear in experimental animals. Acta Otolaryngol Suppl 1972; 305: 29–47PubMedCrossRef

55.

Laurikainen EA, Costa O, Miller JM, et al. Neuronal regulation of cochlear blood flow in the guinea-pig. J Physiol 1994; 480(3): 563–73PubMed

56.

Dziadziola JK, Laurikainen EL, Rachel JD, et al. Betahistine increases vestibular blood flow. Otolaryngol Head Neck Surg 1999; 120: 400–5PubMedCrossRef

57.

Larsen HC, Angelborg C. The vestibular blood flow during CO2 breathing in rabbits. Acta Otolaryngol 1987; 103: 14–17PubMedCrossRef

58.

Raachel JD, Dziadziola JK, Quirk WS. Atrial natriuretic peptide participates in the regulation of vestibular blood flow. Hear Res 1995; 89: 181–6CrossRef

59.

Botta L, Mira E, Valli S, at al. Effects of betahistine on vestibular receptors of the frog. Acta Otolaryngol 1998; 118: 519–23PubMedCrossRef

60.

Housley GD, Norris CH, Guth PS. Histamine and related substances influence neurotransmission in the semicircular canal. Hear Res 1988; 35: 87–98PubMedCrossRef

61.

Tighilet B, Leonard J, Lacour M. Betahistine dihydrochloride treatment facilitates vestibular compensation in the cat. J Vestib Res 1995; 5: 53–66PubMedCrossRef

62.

Tighilet B, Lacour M. Histamine immunoreactivity changes in vestibular-lesioned and histaminergic-treated cats. Eur J Pharmacol 1997; 330: 65–77PubMedCrossRef

63.

Kawabata A, Sasa M, Kishimoto T, et al. Effects of anti-vertigo drugs on medial vestibular neurons activated by horizontal rotation. Jpn J Pharmacol 1991; 55: 101–6PubMedCrossRef

64.

Unemoto H, Sasa M, Takaori S, et al. Inhibitory effect of betahistine on polysynaptic neurons in the lateral vestibular nucleus. Arch Otorhinolaryngol 1982; 236(3): 229–36PubMedCrossRef

65.

Kingma H, Bonink M, Meulenbroeks A, et al. The dose-dependent effect of betahistine on vestibulo-ocular reflex: a double-blind, placebo controlled study in patients with paroxysmal vertigo. Acta Otolaryngologica (Stockh) 1997; 117: 1–6CrossRef

66.

Constantinescu L, Schneider D, Claussen CF. The influence of betahistine on the vestibular evoked potentials in patients with peripheral vestibular disorders. In: 3rd European Federation of the Oto-Rhino-Laryngological Societies (EUFOS); 1996 Jun 9–12; Budapest. Bologna: Monduzzi Editore: 95-8

67.

Oosterveld WJ. Effect of betahistine dihydrochloride on induced vestibular nystagmus: a double blind study. Clin Otolaryngol 1987; 12: 131–5PubMedCrossRef

68.

Betts T, Harris D, Gadd E. The effects of two anti-vertigo drugs (betahistine and prochlorperazine) on driving skills. Br J Clin Pharmacol 1991; 32: 455–8PubMedCrossRef

69.

Xerri C, Lacour M. Compensation deficits in posture and kinetics following unilateral vestibular neurectomy in cats. The role of sensorimotor activity [in French]. Acta Otolaryngol 1980; 90(5–6): 414–24PubMedCrossRef

70.

Zennou-Azogui Y, Borel L, Lacour M, et al. Recovery of head postural control following unilateral vestibular neurectomy in the cat: neck muscle activity and neuronal correlates in Deiters’ nuclei. Acta Otolaryngol Suppl 1993; 509: 1–19PubMed

Titel: Histamine and Betahistine in the Treatment of Vertigo
Elucidation of Mechanisms of Action
verfasst von: Dr Michel Lacour
Olivier Sterkers
Publikationsdatum: 01.11.2001
Verlag: Springer International Publishing
Erschienen in: CNS Drugs / Ausgabe 11/2001
Print ISSN: 1172-7047
Elektronische ISSN: 1179-1934
DOI: https://doi.org/10.2165/00023210-200115110-00004

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Was nützt die Kraniektomie bei schwerer tiefer Hirnblutung?

17.05.2024 Hirnblutung Nachrichten

Eine Studie zum Nutzen der druckentlastenden Kraniektomie nach schwerer tiefer supratentorieller Hirnblutung deutet einen Nutzen der Operation an. Für überlebende Patienten ist das dennoch nur eine bedingt gute Nachricht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 11/2001

Reducing Bleeding Complications After Thrombolytic Therapy for Stroke

Multiple System Atrophy

Autism and Measles-Mumps-Rubella Vaccination