Sandbox42: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 19: | Line 19: | ||
== '''Introduction''' == | == '''Introduction''' == | ||
The drug ketamine is used for medicinal purposes and also, because of its hallucinatory effects, used recreationally. Ketamine is classified as an NMDA receptor antagonist. Glutamate is released and then binds to the NMDA receptor. This triggers the opening of the ion channel. However in the ionotropic pore there are magnesium ions, which greatly limits the ion flow.(1) To counter this the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor also binds glutamate and flows freely. A voltage is built up by the flowing of sodium and potassium ions that eventually expels the magnesium, allowing for | The drug ketamine is used for medicinal purposes and also, because of its hallucinatory effects, used recreationally. Ketamine is classified as an NMDA receptor antagonist. Glutamate is released and then binds to the NMDA receptor. This triggers the opening of the ion channel. However in the ionotropic pore there are magnesium ions, which greatly limits the ion flow.(1) To counter this the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor also binds glutamate and flows freely. A voltage is built up by the flowing of sodium and potassium ions that eventually the post-synaptic cell gets depolarized and expels the magnesium, allowing for sodium, potassium, and calium ions to pass through.(2) | ||
When ketamine binds to the NMDA receptor, the ion channel becomes plugged whether or not the magnesium is expelled, in particular blocking the flow of calcium. This means more AMPA receptors would be created, as well as Kainate receptors, which are also glutamate receptors that are not open as long. | When ketamine binds to the NMDA receptor, the ion channel becomes plugged whether or not the magnesium is expelled, in particular blocking the flow of calcium. This means more AMPA receptors would be created, as well as Kainate receptors, which are also glutamate receptors that are not open as long.(6) Ions that pass through the NMDA receptor also modulate the activity of the receptor. In addition, calcium ions fucntion in the signaling pathway as a second messenger. In that respect, the blocking of the NMDA receptor has been known to cause problems with memory.(3) In fact katamine and PCP, another NMDA receptor antagonist drug, were used to model the hypoglutamate state of schizophrenia.(4) | ||
Today, ketamine is primarily used as a general anesthetic, but is also used as an analgesic and a bronchodilator to help breathing. It has even been proven effective in decreasing depression symptoms that accompany bipolar disorder.(5) In knowing in greater detail the structure and function of | Today, ketamine is primarily used as a general anesthetic, but is also used as an analgesic and a bronchodilator to help breathing. It has even been proven effective in decreasing depression symptoms that accompany bipolar disorder.(5) In knowing in greater detail the structure and function of the NMDA receptor, as well as other receptors, we can gather a better understanding of how drugs like ketamine and PCP effect the body by binding to this site. | ||
| Line 98: | Line 98: | ||
== '''References''' == | == '''References''' == | ||
# "NMDA receptor subunits: function and pharmacology" | # Paoletti P, Neyton J. "NMDA receptor subunits: function and pharmacology" Curr Opin Pharmacol vol 7 (1), 39–47, February 2007. | ||
# "Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones" | # Mark L. Mayer, Gary L. Westbrook, Peter B. Guthrie. "Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones" Nature vol 309, 261 - 263, 17 May 1984. | ||
# "Clinical Implications of Basic Research: Memory and the NMDA receptors" | # Fei Li and Joe Z. Tsien. "Clinical Implications of Basic Research: Memory and the NMDA receptors" New England Journal of Medicine, 361:302, July 16, 2009 | ||
# "NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5- | # S Kapur1, P Seeman. "NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors implications for models of schizophrenia" Molecular Psychiatry vol 7, 8, 837-844, 2002. | ||
# "A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression" | # Nancy Diazgranados et al. "A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression" Archives of General Psychiatry vol 67 (8), 793–802, August 2010. | ||
# Huettner JE. "Kainate receptors and synaptic transmission" Prog. Neurobiol. vol 70 (5), 387–407, 2003. | |||
# "Structure of the zinc-bound amino-terminal domain of the NMDA receptor NR2B subunit" | # "Structure of the zinc-bound amino-terminal domain of the NMDA receptor NR2B subunit" | ||
# http://chemwiki.ucdavis.edu/Wikitexts/Truman_Chem_421%3A_Nagan/N-Methyl-D-Aspartate_Receptor#Subunits | # http://chemwiki.ucdavis.edu/Wikitexts/Truman_Chem_421%3A_Nagan/N-Methyl-D-Aspartate_Receptor#Subunits | ||
