Glutamate Blockers for Vertigo
C. Hain, MD • Marcello Cherchi, M.D., Ph.D.
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Page last modified:
April 25, 2022
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.
- Assarzadegan, F. and M. Sistanizad (2017). "Tolerability and Efficacy of Memantine as Add on Therapy in Patients with Migraine." Iran J Pharm Res 16(2): 791-797.
- Bigal, M., A. Rapoport, F. Sheftell, D. Tepper and S. Tepper (2008). "Memantine in the preventive treatment of refractory migraine." Headache 48(9): 1337-1342.
- Charles, A., C. Flippen, M. Romero Reyes and K. C. Brennan (2007). "Memantine for prevention of migraine: a retrospective study of 60 cases." J Headache Pain 8(4): 248-250.
- Dayanithi, G., G. Desmadryl, C. Travo, C. Chabbert and A. Sans (2007). "Trimetazidine modulates AMPA/kainate receptors in rat vestibular ganglion neurons." Eur J Pharmacol 574(1): 8-14.
- Deakin, J. F., et al. (2008). "Glutamate and the neural basis of the subjective effects of ketamine: a pharmaco-magnetic resonance imaging study." Arch Gen Psychiatry 65(2): 154-164.
- Ehrenberger, K. (2002). "Clinical experience with caroverine in inner ear diseases." Adv Otorhinolaryngol 59: 156-162.
- Hoffmann, J. and A. Charles (2018). "Glutamate and Its Receptors as Therapeutic Targets for Migraine." Neurotherapeutics 15(2): 361-370.
- Huang, L., M. Bocek, J. K. Jordan and A. H. Sheehan (2014). "Memantine for the prevention of primary headache disorders." Ann Pharmacother 48(11): 1507-1511.
- Kumar, A., S. Thomas, R. McLean, F. A. Proudlock, E. Roberts, M. Boggild and I. Gottlob (2009). "Treatment of acquired periodic alternating nystagmus with memantine: a case report." Clin Neuropharmacol 32(2): 109-110.
- Mistry, V. M., P. L. Morizio, M. J. Pepin, W. E. Bryan and J. N. Brown (2021). "Role of memantine in the prophylactic treatment of episodic migraine: A systematic review." Headache 61(8): 1207-1213.
- Noruzzadeh, R., A. Modabbernia, V. Aghamollaii, M. Ghaffarpour, M. H. Harirchian, S. Salahi, N. Nikbakht, N. Noruzi and A. Tafakhori (2016). "Memantine for Prophylactic Treatment of Migraine Without Aura: A Randomized Double-Blind Placebo-Controlled Study." Headache 56(1): 95-103.
- Oestreicher, E., et al. (2002). "Different action of memantine and caroverine on glutamatergic transmission in the mammalian cochlea." Adv Otorhinolaryngol 59: 18-25.
- Shanmugam, S., K. Karunaikadal, S. Varadarajan and M. Krishnan (2019). "Memantine Ameliorates Migraine Headache." Ann Indian Acad Neurol 22(3): 286-290.
- Spengos, K., C. Theleritis and T. Paparrigopoulos (2008). "Memantine and NMDA antagonism for chronic migraine: a potentially novel therapeutic approach?" Headache 48(2): 284-286.
- Starck, M., H. Albrecht, W. Pollmann, M. Dieterich and A. Straube (2010). "Acquired pendular nystagmus in multiple sclerosis: an examiner-blind cross-over treatment study of memantine and gabapentin." J Neurol 257(3): 322-327.
- Krymchantowski, A. and C. Jevoux (2009). "Memantine in the preventive treatment for migraine and refractory migraine." Headache 49(3): 481-482.
Thurtell, M. J., A. C. Joshi, A. C. Leone, R. L. Tomsak, G. S. Kosmorsky, J. S. Stahl and R. J. Leigh (2010). "Crossover trial of gabapentin and memantine as treatment for acquired nystagmus." Ann Neurol 67(5): 676-680.
- Xu, Z., L. Chen, S. Jin, X. Chen and B. Yang (2021). "The Efficacy of Memantine for the Treatment of Migraine: A Meta-Analysis of Randomized Controlled Studies." Clin Neuropharmacol 44(3): 94-98.