Reuptake inhibitor: Difference between revisions

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==Mechanism of action==

[[File:Reuptake inhibitor.png|350px|thumb|right|The effect of reuptake inhibitors on the presynaptic neurone]]

Standard reuptake inhibitors are believed to function by binding directly to the transporter protein of the [[neurotransmitter]] in question.<ref> Ravna AW, Sylte I, Dahl SG (2003). "Molecular mechanism of citalopram and cocaine interactions with neurotransmitter transporters.". J Pharmacol Exp Ther. 307 (1): 34–41. | https://www.ncbi.nlm.nih.gov/pubmed/12944499</ref> By occupying the transporter, a reuptake inhibitor competitively blocks its respective neurotransmitter from binding to the transporter protein and thus prevents it from being transported from the synapse into the presynaptic neurone. Reuptake inhibitors, like [[agonists]] and [[antagonists]], are an example of ligand-receptor binding.

Standard reuptake inhibitors are believed to function by binding directly to the transporter protein of the [[neurotransmitter]] in question.<ref> Ravna AW, Sylte I, Dahl SG (2003). "Molecular mechanism of citalopram and cocaine interactions with neurotransmitter transporters.". J Pharmacol Exp Ther. 307 (1): 34–41. | https://www.ncbi.nlm.nih.gov/pubmed/12944499</ref> By occupying the transporter, a reuptake inhibitor competitively blocks its respective neurotransmitter from binding to the transporter protein and thus prevents it from being transported from the synapse into the presynaptic neurone. Reuptake inhibitors, like [[agonists]] and [[antagonists]], are an example of ligand-receptor binding.<ref>Dunn, Michael F(Apr 2010) Protein–Ligand Interactions: General Description. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001340.pub2]</ref>

Alternatively, some reuptake inhibitors bind to allosteric sites and inhibit reuptake indirectly and noncompetitively. Allosteric binding may cause a conformational change in the transporter protein that prevents it from reuptaking its respective neurotransmitter. Several [[dissociative]] drugs have been shown to work this way, including [[Phencyclidine|PCP]] and related drugs [[ketamine]], and [[dizocilpine]] (MK-801). They appear to exert their reuptake inhibition by binding to allosteric sites on each of the respective monoamine transporters. In addition to their high affinity for the main site of the monoamine transporters, several competitive transporter substrates, such as [[cocaine]], have lower affinity for these allosteric sites as well.

Alternatively, some reuptake inhibitors bind to allosteric sites and inhibit reuptake indirectly and noncompetitively. Allosteric binding may cause a conformational change in the transporter protein that prevents it from reuptaking its respective neurotransmitter.<ref>Dynamics, flexibility and ligand-induced conformational changes in biological macromolecules: a computational approach. | http://www.ncbi.nlm.nih.gov/pubmed/22098354</ref> Several [[dissociative]] drugs have been shown to work this way, including [[Phencyclidine|PCP]] and related drugs [[ketamine]], and [[dizocilpine]] (MK-801). <ref>Akunne HC, Reid AA, Thurkauf A, Jacobson AE, de Costa BR, Rice KC, Heyes MP, Rotman RB (1991). "[3H]1-[2-(2-thienyl)cyclohexyl]piperidine labels two high-affinity binding sites in human cortex: further evidence for phencyclidine binding sites associated with the biogenic amine reuptake complex.". Synapse. 8 (4): 289–300. | https://www.ncbi.nlm.nih.gov/pubmed/1833849</ref> They appear to exert their reuptake inhibition by binding to allosteric sites on each of the respective monoamine transporters. In addition to their high affinity for the main site of the monoamine transporters, several competitive transporter substrates, such as [[cocaine]], have lower affinity for these allosteric sites as well.

==Types of reuptake inhibitors==

@@ Line 5: / Line 5: @@
 ==Mechanism of action==
 [[File:Reuptake inhibitor.png|350px|thumb|right|The effect of reuptake inhibitors on the presynaptic neurone]]
-Standard reuptake inhibitors are believed to function by binding directly to the transporter protein of the [[neurotransmitter]] in question.<ref> Ravna AW, Sylte I, Dahl SG (2003). "Molecular mechanism of citalopram and cocaine interactions with neurotransmitter transporters.". J Pharmacol Exp Ther. 307 (1): 34–41. | https://www.ncbi.nlm.nih.gov/pubmed/12944499</ref> By occupying the transporter, a reuptake inhibitor competitively blocks its respective neurotransmitter from binding to the transporter protein and thus prevents it from being transported from the synapse into the presynaptic neurone. Reuptake inhibitors, like [[agonists]] and [[antagonists]], are an example of ligand-receptor binding.
+Standard reuptake inhibitors are believed to function by binding directly to the transporter protein of the [[neurotransmitter]] in question.<ref> Ravna AW, Sylte I, Dahl SG (2003). "Molecular mechanism of citalopram and cocaine interactions with neurotransmitter transporters.". J Pharmacol Exp Ther. 307 (1): 34–41. | https://www.ncbi.nlm.nih.gov/pubmed/12944499</ref> By occupying the transporter, a reuptake inhibitor competitively blocks its respective neurotransmitter from binding to the transporter protein and thus prevents it from being transported from the synapse into the presynaptic neurone. Reuptake inhibitors, like [[agonists]] and [[antagonists]], are an example of ligand-receptor binding.<ref>Dunn, Michael F(Apr 2010) Protein–Ligand Interactions: General Description. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001340.pub2]</ref>
-Alternatively, some reuptake inhibitors bind to allosteric sites and inhibit reuptake indirectly and noncompetitively. Allosteric binding may cause a conformational change in the transporter protein that prevents it from reuptaking its respective neurotransmitter. Several [[dissociative]] drugs have been shown to work this way, including [[Phencyclidine|PCP]] and related drugs [[ketamine]], and [[dizocilpine]] (MK-801). They appear to exert their reuptake inhibition by binding to allosteric sites on each of the respective monoamine transporters. In addition to their high affinity for the main site of the monoamine transporters, several competitive transporter substrates, such as [[cocaine]], have lower affinity for these allosteric sites as well.
+Alternatively, some reuptake inhibitors bind to allosteric sites and inhibit reuptake indirectly and noncompetitively. Allosteric binding may cause a conformational change in the transporter protein that prevents it from reuptaking its respective neurotransmitter.<ref>Dynamics, flexibility and ligand-induced conformational changes in biological macromolecules: a computational approach. | http://www.ncbi.nlm.nih.gov/pubmed/22098354</ref> Several [[dissociative]] drugs have been shown to work this way, including [[Phencyclidine|PCP]] and related drugs [[ketamine]], and [[dizocilpine]] (MK-801). <ref>Akunne HC, Reid AA, Thurkauf A, Jacobson AE, de Costa BR, Rice KC, Heyes MP, Rotman RB (1991). "[3H]1-[2-(2-thienyl)cyclohexyl]piperidine labels two high-affinity binding sites in human cortex: further evidence for phencyclidine binding sites associated with the biogenic amine reuptake complex.". Synapse. 8 (4): 289–300. | https://www.ncbi.nlm.nih.gov/pubmed/1833849</ref>  They appear to exert their reuptake inhibition by binding to allosteric sites on each of the respective monoamine transporters. In addition to their high affinity for the main site of the monoamine transporters, several competitive transporter substrates, such as [[cocaine]], have lower affinity for these allosteric sites as well.
 ==Types of reuptake inhibitors==