Ketamine Essay

755 Words4 Pages
Chronic intake, the delayed onset of action, drug resistance and numerous side effects force the researchers to look for the new, safe antidepressant strategies (1, 2) with rapid onset and longer time of action.
Results obtained in the recent years give some hope that ketamine which is a global NMDAR antagonist could be the fast and long- acting novel antidepressant. Antidepressant–like activity of ketamine was shown in many preclinical studies (1–7). The single non-anesthetic dose of ketamine reversed symptoms of major depression (MDD) in clinical conditions (8). These antidepressant effects of ketamine also occurred in patients who suffered from resistant depression or suicidal ideations (9–12). Despite a successful
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At the molecular level of explanation these processes are dependent on the interplay between glutamate receptors, Ca2+ channels, the increase of intracellular Ca2+ levels, Ca2+-dependent proteins like Akt, ERK, mTOR and neurotrophins such as brain derived neurotrophic factor (BDNF) (24, 25).
Because Ca2+ is the central point for all mentioned processes, we focused our interests on hyperforin which is Ca2+-modulator. Hyperforin is the natural and biologically active compound extracted from Hypericum Perforatum (St John Wort) (26). The St John Wort extract and hyperforin attenuated symptoms of mild to moderate depression in a few clinical trials. Both extract and hyperforin displayed antidepressant-like activity in preclinical studies (27, 28).
From molecular perspective, hyperforin has multidirectional mechanisms 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 increased an inward Ca2+ current. These processes are dose dependent and probably involved a few different cellular events. In the details, hyperforin in in vitro studies increased the Ca2+ intracellular level by activation of the non-selective canonical transient receptor potential 6 channels (TRPC6) or by the releasing Ca2+ from mitochondria (32–34). As has been previously shown hyperforin activates intracellular
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