Reuptake inhibitor: Difference between revisions

A '''reuptake inhibitor''', also known as a transporter blocker, is a drug that inhibits the reuptake of a [[neurotransmitter]] from the synapse into the presynaptic neurone, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore an increase in neurotransmission. Various drugs utilize reuptake inhibition to exert their psychological and physiological effects, including many [[antidepressants]] and [[stimulants]].

Most known reuptake inhibitors affect the monoamine neurotransmitters [[serotonin]], [[noradrenaline]] (and [[adrenaline]]), and [[dopamine]]. However, there are also a number of pharmaceuticals and [[research chemicals]] that act as reuptake inhibitors for other neurotransmitters such as [[glutamate]], [[GABA]], glycine, adenosine, choline (the precursor of [[acetylcholine]]), and the endocannabinoids.

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.<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.

*A '''selective reuptake inhibitor''' will inhibit the reuptake of a specific [[neurotransmitter]] with negligible or no effects on the reuptake of other neurotransmitters. An example of this is the class of antidepressants known as selective serotonin reuptake inhibitors, or [[SSRIs]]. SSRIs solely target serotonin transporters (SERTs), blocking the reuptake of serotonin, and increasing extracellular concentrations of the neurotransmitter.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896866/</ref>

*A '''non-selective reuptake inhibitor''' will inhibit the reuptake of more than one type of [[neurotransmitter]]. An example of this is [[cocaine]], which acts as a serotonin-noradrenaline-dopamine reuptake inhibitor, or [[SNDRI]]. Ketamine is an example of a weak SNDRI, it is non-selective because it affects the reuptake of multiple neurotransmitters.<ref>Kohrs, R; Durieux, ME (November 1998). "Ketamine: Teaching an old drug new tricks". Anesthesia & Analgesia | https://www.ncbi.nlm.nih.gov/pubmed/9806706</ref>

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