Table 3 Description of NMDA antagonists and mechanism of action(s)
From: NMDA antagonists for treating the non-motor symptoms in Parkinson’s disease
Drug, indication | Mechanism of action |
|---|---|
Dextromethorphan, rapid antidepressant | Putative NMDA-2A/2B-receptor antagonist NMDA-3A antagonist Opioid sigma 1 and sigma 2 receptor agonists mTOR activation Alpha 3/beta 4 nicotinic receptor antagonist Targets the serotonin reuptake pump Putative AMPA activation |
Ketamine, rapid antidepressant and pain, anesthetic agent | NMDA-3A receptor antagonist Substance P receptor antagonist—probably associated with G proteins that activate a phosphatidylinositol–calcium second messenger system D2 dopamine receptor agonist/partial agonist Kappa-opioid receptor agonist; Mu/delta-opioid receptor binder 5-hydroxytryptamine receptor 1 & 2 antagonist Muscarinic acetylcholine receptor binder Induction of BDNF expression mTOR modulation and activation |
Amantadine, treats drug-induced extrapyramidal reactions | NMDA receptor antagonist D2 receptor agonist—mediated by G proteins which inhibit adenylyl cyclase Matrix protein 2 inhibitor for Influenza A virus |
Memantine, treats moderate to severe cognitive impairment | NMDA-3A antagonist NMDA-2A/2B-receptor antagonist NMDA-1 binder D2 dopamine receptor agonist 5-hydroxytryptamine receptor 3A antagonist Alpha-7 nicotinic cholinergic receptor subunit antagonist |
D-cycloserine, second-line agent for drug-resistant tuberculosis; cognition enhancer | Putative cyclic NMDA partial agonist Glycine site partial agonist Inhibits cell-wall biosynthesis in bacteria Alanine racemase inhibitor |
Dizocilpine (MK-801), potent anticonvulsant | Noncompetitive NMDA receptor antagonist Inhibits reuptake of dopamine, noradrenaline, and serotonin Nicotinic acetylcholine receptor antagonist |
