Ketamine Essay

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Introduction Chronic intake, delayed onset of action, drug resistance and numerous side effects of current antidepressants have forced researchers to look for new and safer drugs (1, 2) with rapid onset and longer acting times. Results obtained in recent years have been encouraging, especially with ketamine a global NMDAR antagonist. The antidepressant-like activity of ketamine has been shown in many preclinical studies (1–7). A single non-anesthetic dose of ketamine reversed the symptoms of clinical major depression (MDD) (8). The antidepressant effects of ketamine were also observed in patients who suffered from treatment-resistant depression or suicidal ideations (9–12). Despite successful clinical trials with ketamine, its use on a…show more content…
Because Ca2+ is the focal point to all the processes mentioned above, we have focused our study on hyperforin a Ca2+-modulator. Hyperforin is the natural and biologically active compound extracted from Hypericum perforatum (St John’s Wort) (26). Both St John’s Wort and hyperforin attenuated symptoms of mild to moderate depression in a few clinical trials and displayed antidepressant-like activity in preclinical studies (27, 28). From a molecular perspective, hyperforin has a multi-directional mechanism of action. It acts on ligand-gated (GABA, NMDA, and AMPA receptors) (29, 30) and voltage-gated channels (Ca2+, K+, and Na+) (29, 31). In contrast to blockade of ion transport through the plasma membrane, hyperforin can increase inward Ca2+ currents. These processes are dose-dependent and may involve different cellular events. In vitro studies have shown that hyperforin increases intracellular Ca2+ levels by the activation of the non-selective canonical transient receptor potential 6 channel (TRPC6) or by releasing Ca2+ from the mitochondria (32–34). As has been previously shown, hyperforin activates intracellular signaling pathways leading to changes in intracellular Ca2+ levels. Leuner et al. showed that hyperforin increased the
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