Abstract
Migraine is a debilitating disorder affecting females more frequently than males. There is some evidence that drugs targeting glutamate receptors: memantine and ketamine might be beneficial in the therapy of this entity. Therefore, the purpose of this work is to present NMDA receptor antagonists, memantine and ketamine, as potential anti-migraine agents. We searched PubMed/MEDLINE, Embase, and clinical trials submitted to ClinicalTrials.gov to find publications describing eligible trials published between database inception and December 31, 2021. This comprehensive literature review summarizes data on the use of the NMDA receptor antagonists memantine and ketamine in the pharmacotherapy of migraine. Results from 20 previous and recent preclinical experiments are discussed and correlated with 19 clinical trials (including case series, open-label, and randomized placebo-controlled trials). For the purposes of this review, the authors hypothesized that the propagation of SD is a major mechanism in the pathophysiology of migraine. In several animal studies and in vitro studies, memantine and ketamine inhibited or reduced propagation of the SD. In addition, the results of clinical trials suggest that memantine or ketamine may be an effective treatment option for migraine. However, most studies on these agents lack control group. Although further clinical trials are needed, the results suggest that ketamine or memantine may be promising molecules for the treatment of severe migraine. Particular attention should be paid to people who have a treatment-resistant form of migraine with aura or have exhausted existing treatment options. For them, the drugs under discussion could represent an interesting alternative in the future.
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Abbreviations
- 5-HT:
-
5-Hydroxytryptamine, serotonin
- AMPA:
-
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
- BDNF:
-
Brain-derived neurotrophic factor
- CGRP:
-
Calcitonin gene–related peptide
- CNS:
-
Central nervous system
- CSF:
-
Cerebrospinal fluid
- CVDs:
-
Cardiovascular diseases
- ER:
-
Extended release
- HADS :
-
Hospital anxiety and depression scale
- HD:
-
Headache diaries
- ICHD-3:
-
International Classification of Headache Disorders, 3rd edition
- iGlu:
-
Ionotropic glutamate
- IM:
-
Intramuscularly
- IN:
-
Intranasal
- IOS:
-
Intrinsic optical signal
- IP:
-
Intraperitoneal
- IV:
-
Intravenous
- LC:
-
Locus coeruleus
- LTP:
-
Long-term potentiation
- MDD:
-
Major depressive disorder
- mGlu:
-
Metabotropic glutamate
- MIDAS:
-
Migraine disability assessment
- MRN:
-
Nucleus raphe magnus
- nACh:
-
Nicotinic acetylcholine
- NMDA:
-
N-methyl-D-aspartic acid
- NRS:
-
Numeric Rating Scale
- NSAIDs:
-
Nonsteroidal anti-inflammatory drugs
- PAG:
-
Periaqueductal gray
- PSQI:
-
Pittsburgh sleep quality index
- SAH:
-
Subarachnoid hemorrhage
- SC:
-
Subcutaneous
- SD:
-
Cortical spreading depression
- SF-12:
-
Short-form 12
- SERSDA:
-
Side Effects Rating Scale for Dissociative Anaesthetics
- SSRIs:
-
Serotonin reuptake inhibitors
- TBI:
-
Traumatic brain injury
- TCAs:
-
Tricyclic antidepressants
- TNC:
-
Trigeminal nucleus caudalis
- VAS:
-
Visual analogue scale
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Podkowa, K., Czarnacki, K., Borończyk, A. et al. The NMDA receptor antagonists memantine and ketamine as anti-migraine agents. Naunyn-Schmiedeberg's Arch Pharmacol 396, 1371–1398 (2023). https://doi.org/10.1007/s00210-023-02444-2
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DOI: https://doi.org/10.1007/s00210-023-02444-2