Glutamate Blockers for Vertigo

Timothy C. Hain, MDMarcello Cherchi, M.D., Ph.D.

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There are only a few glutamate blockers used in clinical medicine


Memantine received FDA approval in the United States for the treatment of Alzheimer's disease, though it has also been studied (in off-label usage) in autism and bipolar disorder. Memantine is an uncompetitive antagonist at glutamatergic NMDA receptors, inhibiting influx of calcium ions. Since glutamate is an excitatory neurotransmitter, and since memantine inhibits glutamatergic NMDA receptors, it is thought to protect neurons against "excitotoxicity," or excessive stimulation.

The role of memantine in central vestibular disorders is limited. Several small studies found memantine to be effective in treating various forms of acquired nystagmus (Kumar, Thomas et al. 2009; Starck, Albrecht et al. 2010); Thurtell, Joshi et al. 2010).

There is also a modest literature regarding memantine in the prophylactic treatment of migraine (Charles, Flippen et al. 2007, Bigal, Rapoport et al. 2008, Spengos, Theleritis et al. 2008, Krymchantowski and Jevoux 2009, Huang, Bocek et al. 2014, Noruzzadeh, Modabbernia et al. 2016, Assarzadegan and Sistanizad 2017, Hoffmann and Charles 2018, Rau and Dodick 2019, Shanmugam, Karunaikadal et al. 2019, Mistry, Morizio et al. 2021, Moreno-Ajona, Villar-Martinez et al. 2021, Xu, Chen et al. 2021).

Although some studies describe memantine as well-tolerated (Assarzadegan and Sistanizad 2017), our own experience has been that most patients discontinue the drug due to side effects, often before completing an adequate trial.



This drug is another glutamate blocker, that appears to be a little broader in action than memantine(Oestreicher, E., et al., 2002). It has been tried in Europe. (Ejremnerger, 2002) It is somewhat impractical because it has limited uptake with oral administration and needs to be adminiserted intravenously or locally. It has also been tried in tinnitus. There is no literature about it's use for vertigo or nystagamus. Because oral dosing is not possible, the utility of this drug appears limited.

Hallucinogenic NMDA drugs (inhibit glutamate receptor)

These include MK-01, phencyclidine (PCP, "angel dust"), and Ketamine ("special K") among others (Deakin et al, 2008). . Of course, side effects and abuse are a problem. Ketamine produces a general "lack of responsive awareness", as well as dizziness (Soto et al, 2013). There is no rationale for these drugs for treatment of vertigo.