| Mechanisms of action and interaction pathways |
Interacts with NMDA receptors, ion channels, including dopamine, serotonin, sigma, opioid and cholinergic receptors, and cyclic nucleotide-gated (HCN) channels activated by hyperpolarization [2]; Lowers levels of TNF-α, IL-6, IFN-γ, IL-10, IL-1β, and IL-4 in patients exhibiting depressive symptoms and associated pain [2]; Increases synaptogenesis and improves signaling through neurotrophic factors in brain regions [8]; Relief of Mg2+ blockade by membrane depolarization with an influx of sodium and calcium, which is associated with higher-order brain functions, including learning and memory [12].
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| Protective effects on neurodegenerative diseases |
There is little evidence supporting its use in humans for therapeutic purposes; Animal studies have shown increased memory consolidation and cell proliferation [15,16]; Low-dose use in rodents has indicated activity of its metabolites for acute antidysetic and antiparkinsonian activities [19]; Multiple sclerosis shows long-term reductions in fatigue-related symptoms after low-dose ketamine infusions [28,29];
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| Role in acute neuroinflammatory disorders |
Preventing hypotension, reducing fluid use, and preserving spontaneous ventilation, while also offering the potential to optimize analgesia and sedation in management of ventilated patients with traumatic brain injury [31]; Appears to be a safe drug that can be used alone or in combination with other sedatives in patients with moderate to severe spinal cord injury (SCI) who require mechanical ventilation [33,34]; Ketamine has been shown to downregulate several inflammatory cytokines in viral sepsis, including IL-6 [40].
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| Addiction and psychiatric disorders |
Antidepressant and antisuicidal effects in unipolar and bipolar depression, as well as in treatment-resistant depression, with repeated doses extending the duration of efficacy [41]; Potential therapeutic option for patients with treatment-resistant anxiety disorders, particularly obsessive–compulsive disorder and post-traumatic stress disorder [45]; Acts on dopamine system through the effects of local GABA neurons on circuits. The absence of adaptive synaptic plasticity indicates that ketamine dependence is limited by its pharmacology [48];
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| Therapeutic effects as an adjuvant drug in neuroanesthesia |
Its sympathomimetic profile, together with its neuroprotective effect, may be advantageous over other sedative and analgesic drugs used in patients with traumatic brain injury who are at risk of experiencing a reduction in blood pressure [57]; Therapeutic effect in suppressing disseminated depolarization after brain injury, pulmonary vasodilation and bronchodilation, and increased mean arterial pressure and heart rate [58,59,60]; In patients with elevated intracranial pressure (ICP) before anesthesia, its use in traumatic brain injury (TBI) is not indicated [61]; May improve neurological outcomes after cardiac arrest [66]; S-ketamine administered via patient-controlled analgesia reduced opioid consumption in a dose-dependent manner following major lumbar fusion surgery [67]; Attenuation of the opioid-induced hyperalgesic response by N-methyl-D-aspartate (NMDA) blockade [68]; Incorporating ketamine into ERAS strategies in neurosurgery can strengthen them by offering prolonged analgesia and limiting opioid use [69].
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