Reuptake inhibitor
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.
Mechanism of action
Standard reuptake inhibitors are believed to function by binding directly to the transporter protein of the neurotransmitter in question. 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.
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 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.
Types of reuptake inhibitors
- A selective reuptake inhibitor will inhibit the reuptake of a specific neurotransmitter. An example of this is the class of antidepressants known as selective serotonin reuptake inhibitors, or SSRIs.
- 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.
See also
References
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