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Betahistine in the treatment of Ménière's disease.

Lacour M, van de Heyning PH, Novotny M, Tighilet B - Neuropsychiatr Dis Treat (2007)

Bottom Line: Growing evidence suggests that the mechanism of action of betahistine lies in the central nervous system and in particularly in the neuronal systems involved in the recovery from process after vestibular loss.The histaminergic neurones of the tuberomamillary and vestibular nuclei are implicated.Although the results of comparative studies between betahistine and other drugs (flunarizine, cinnarizine, and cinnarizine + dimenhydrate) are equivocal, the efficacy of betahistine is now clear.

View Article: PubMed Central - PubMed

Affiliation: UMR 6149 Université de Provence/CNRS "Neurobiologie Intégrative et Adaptative", Marseille Cedex 3, France. Michel.Lacour@up.univ-mrs.fr

ABSTRACT
Ménière's disease and related disease of the vestibular system are common and debilitating. Current therapy is multi-modal and includes drug therapy and lifestyle adaptations. Unfortunately many of the drugs used in treatment (particularly those used to control nausea) are sedative and hamper the process of vestibular compensation. Although betahistine (Serc®), BetaSerc®); Solvay Pharmaceuticals) is the mainstay of drug treatment in these illnesses, its efficacy has not, until recently, been evaluated to modern standards. Betahistine is an analog of histamine with weak agonist properties at histamine H1 receptors and more potent anatgonistic effects at histamine H3 receptors. Growing evidence suggests that the mechanism of action of betahistine lies in the central nervous system and in particularly in the neuronal systems involved in the recovery from process after vestibular loss. The histaminergic neurones of the tuberomamillary and vestibular nuclei are implicated. In recent years the clinical efficacy of betahistine has been demonstrated in double-blind, randomized, placebo, and active controlled studies in adequate numbers of patients. Although the results of comparative studies between betahistine and other drugs (flunarizine, cinnarizine, and cinnarizine + dimenhydrate) are equivocal, the efficacy of betahistine is now clear.

No MeSH data available.


Related in: MedlinePlus

Quantification of the histidine decarboxylase (HDC) mRNA labeled surface in the right (hatched columns) and left (solid columns) tuberomammillary (TM) nuclei for the two groups of betahistine-treated cats compared with the control, untreated cats (open columns). Note that HDC mRNA labeled surface is significantly increased in the TM nuclei of betahistine-treated cats. ** p < 0.0001.
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f2-ndt-3-429: Quantification of the histidine decarboxylase (HDC) mRNA labeled surface in the right (hatched columns) and left (solid columns) tuberomammillary (TM) nuclei for the two groups of betahistine-treated cats compared with the control, untreated cats (open columns). Note that HDC mRNA labeled surface is significantly increased in the TM nuclei of betahistine-treated cats. ** p < 0.0001.

Mentions: It has clearly been shown that the behavioral recovery process after unilateral vestibular neurectomy (UVN) in the cat is strongly accelerated under betahistine treatment (Tighilet et al 1995). Betahistine treatment reduces the time to recovery by 2 weeks for both static (posture) and kinetic (locomotor equilibrium) functions compared with controls (untreated and double blind, placebo-controlled animals (Figure 1). Immunohistochemical investigations performed in the same cat model suggest that improvement in vestibular compensation is related to changes in HA synthesis and release (Tighilet and Lacour 1997). Further studies using an in situ hybridization method for quantifying the messenger RNA for histidine decarboxylase (HDC), the enzyme synthesizing HA, pointed to an up-regulation of HDC mRNA in the TM nuclei of cats treated with HA-like drugs (Tighilet et al 2002) (Figure 2). In addition, receptor binding studies showed a downregulation of histamine H3 receptors in both the VN and TM nuclei. It seems very likely, therefore, that betahistine upregulates HA turnover by blocking the presynaptic histamine H3 receptors. This hypothesis is corroborated by the well known role of these receptors in mediating autoinhibition of brain HA release (Arrang et al 1983) and autoregulation of HA synthesis (Arrang et al 1987, 1992). In rat brain slices, agonists and antagonists of the histamine H3 receptors reduce and enhance HA release, respectively (Arrang et al 1983, 1987; Garbag et al 1989).


Betahistine in the treatment of Ménière's disease.

Lacour M, van de Heyning PH, Novotny M, Tighilet B - Neuropsychiatr Dis Treat (2007)

Quantification of the histidine decarboxylase (HDC) mRNA labeled surface in the right (hatched columns) and left (solid columns) tuberomammillary (TM) nuclei for the two groups of betahistine-treated cats compared with the control, untreated cats (open columns). Note that HDC mRNA labeled surface is significantly increased in the TM nuclei of betahistine-treated cats. ** p < 0.0001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2655085&req=5

f2-ndt-3-429: Quantification of the histidine decarboxylase (HDC) mRNA labeled surface in the right (hatched columns) and left (solid columns) tuberomammillary (TM) nuclei for the two groups of betahistine-treated cats compared with the control, untreated cats (open columns). Note that HDC mRNA labeled surface is significantly increased in the TM nuclei of betahistine-treated cats. ** p < 0.0001.
Mentions: It has clearly been shown that the behavioral recovery process after unilateral vestibular neurectomy (UVN) in the cat is strongly accelerated under betahistine treatment (Tighilet et al 1995). Betahistine treatment reduces the time to recovery by 2 weeks for both static (posture) and kinetic (locomotor equilibrium) functions compared with controls (untreated and double blind, placebo-controlled animals (Figure 1). Immunohistochemical investigations performed in the same cat model suggest that improvement in vestibular compensation is related to changes in HA synthesis and release (Tighilet and Lacour 1997). Further studies using an in situ hybridization method for quantifying the messenger RNA for histidine decarboxylase (HDC), the enzyme synthesizing HA, pointed to an up-regulation of HDC mRNA in the TM nuclei of cats treated with HA-like drugs (Tighilet et al 2002) (Figure 2). In addition, receptor binding studies showed a downregulation of histamine H3 receptors in both the VN and TM nuclei. It seems very likely, therefore, that betahistine upregulates HA turnover by blocking the presynaptic histamine H3 receptors. This hypothesis is corroborated by the well known role of these receptors in mediating autoinhibition of brain HA release (Arrang et al 1983) and autoregulation of HA synthesis (Arrang et al 1987, 1992). In rat brain slices, agonists and antagonists of the histamine H3 receptors reduce and enhance HA release, respectively (Arrang et al 1983, 1987; Garbag et al 1989).

Bottom Line: Growing evidence suggests that the mechanism of action of betahistine lies in the central nervous system and in particularly in the neuronal systems involved in the recovery from process after vestibular loss.The histaminergic neurones of the tuberomamillary and vestibular nuclei are implicated.Although the results of comparative studies between betahistine and other drugs (flunarizine, cinnarizine, and cinnarizine + dimenhydrate) are equivocal, the efficacy of betahistine is now clear.

View Article: PubMed Central - PubMed

Affiliation: UMR 6149 Université de Provence/CNRS "Neurobiologie Intégrative et Adaptative", Marseille Cedex 3, France. Michel.Lacour@up.univ-mrs.fr

ABSTRACT
Ménière's disease and related disease of the vestibular system are common and debilitating. Current therapy is multi-modal and includes drug therapy and lifestyle adaptations. Unfortunately many of the drugs used in treatment (particularly those used to control nausea) are sedative and hamper the process of vestibular compensation. Although betahistine (Serc®), BetaSerc®); Solvay Pharmaceuticals) is the mainstay of drug treatment in these illnesses, its efficacy has not, until recently, been evaluated to modern standards. Betahistine is an analog of histamine with weak agonist properties at histamine H1 receptors and more potent anatgonistic effects at histamine H3 receptors. Growing evidence suggests that the mechanism of action of betahistine lies in the central nervous system and in particularly in the neuronal systems involved in the recovery from process after vestibular loss. The histaminergic neurones of the tuberomamillary and vestibular nuclei are implicated. In recent years the clinical efficacy of betahistine has been demonstrated in double-blind, randomized, placebo, and active controlled studies in adequate numbers of patients. Although the results of comparative studies between betahistine and other drugs (flunarizine, cinnarizine, and cinnarizine + dimenhydrate) are equivocal, the efficacy of betahistine is now clear.

No MeSH data available.


Related in: MedlinePlus