Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal or glial cell after it has performed its function of transmitting a neural impulse.
Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. Off-label uses include treatments for attention-deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and migraine prevention. SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which act upon single neurotransmitters.
A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.
A norepinephrine reuptake inhibitor or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline) by blocking the action of the norepinephrine transporter (NET). This in turn leads to increased extracellular concentrations of norepinephrine and epinephrine and therefore can increase adrenergic neurotransmission.
The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene.
(+)-CPCA is a stimulant drug similar in structure to pethidine and to RTI-31, but nocaine lacks the two-carbon bridge of RTI-31's tropane skeleton. This compound was first developed as a substitute agent for cocaine.
A serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), also known as a triple reuptake inhibitor (TRI), is a type of drug that acts as a combined reuptake inhibitor of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine. It does this by concomitantly inhibiting the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), respectively. Inhibition of the reuptake of these neurotransmitters increases their extracellular concentrations and, therefore, results in an increase in serotonergic, adrenergic, and dopaminergic neurotransmission. The naturally-occurring and potent SNDRI cocaine is widely used recreationally and often illegally for the euphoric effects it produces.
A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin by blocking the action of the serotonin transporter (SERT). This in turn leads to increased extracellular concentrations of serotonin and, therefore, an increase in serotonergic neurotransmission. It is a type of monoamine reuptake inhibitor (MRI); other types of MRIs include dopamine reuptake inhibitors and norepinephrine reuptake inhibitors.
Ethylphenidate (EPH) is a psychostimulant and a close analog of methylphenidate.
Nisoxetine, originally synthesized in the Lilly research laboratories during the early 1970s, is a potent and selective inhibitor for the reuptake of norepinephrine (noradrenaline) into synapses. It currently has no clinical applications in humans, although it was originally researched as an antidepressant. Nisoxetine is now widely used in scientific research as a standard selective norepinephrine reuptake inhibitor. It has been used to research obesity and energy balance, and exerts some local analgesia effects.
Reuptake inhibitors (RIs) are a type of reuptake modulators. It is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.
Difluoropine (O-620) is a stimulant drug synthesised from tropinone, which acts as a potent and selective dopamine reuptake inhibitor. Difluoropine is unique among the tropane-derived dopamine reuptake inhibitors in that the active stereoisomer is the (S) enantiomer rather than the (R) enantiomer, the opposite way round compared to natural cocaine. It is structurally related to benztropine and has similar anticholinergic and antihistamine effects in addition to its dopamine reuptake inhibitory action.
Ciclazindol (WY-23409) is an antidepressant and anorectic drug of the tetracyclic chemical class that was developed in the mid to late 1970s, but was never marketed. It acts as a norepinephrine reuptake inhibitor, and to a lesser extent as a dopamine reuptake inhibitor. Ciclazindol has no effects on the SERT, 5-HT receptors, mACh receptors, or α-adrenergic receptors, and has only weak affinity for the H1 receptor. As suggested by its local anesthetic properties, ciclazindol may also inhibit sodium channels. It is known to block potassium channels as well.
A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain. No selective and robust DRAs are currently known. On the other hand, many releasing agents of both dopamine and norepinephrine and of serotonin, norepinephrine, and dopamine are known. Serotonin–dopamine releasing agents (SDRAs), for instance 5-chloro-αMT, are much more rare and are not selective for dopamine release but have also been developed. Examples of major NDRAs include the psychostimulants amphetamine and methamphetamine, while an example of an SNDRA is the entactogen methylenedioxymethamphetamine (MDMA). These drugs are frequently used for recreational purposes and encountered as drugs of abuse. Selective DRAs, as well as NDRAs, have medical applications in the treatment of attention deficit hyperactivity disorder (ADHD).
JNJ-7925476 is a triple reuptake inhibitor antidepressant discovered by Johnson & Johnson, but never marketed.
A serotonin–dopamine reuptake inhibitor (SDRI) is a type of drug which acts as a reuptake inhibitor of the monoamine neurotransmitters serotonin and dopamine by blocking the actions of the serotonin transporter (SERT) and dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of serotonin and dopamine, and, therefore, an increase in serotonergic and dopaminergic neurotransmission.
A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine transporters (MATs), which include the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT). This in turn results in an increase in the synaptic concentrations of one or more of these neurotransmitters and therefore an increase in monoaminergic neurotransmission.
Pseudophenmetrazine is a psychostimulant compound of the morpholine class. It is the N-demethylated and cis-configured analogue of phendimetrazine as well as the cis-configured stereoisomer of phenmetrazine. In addition, along with phenmetrazine, it is believed to be one of the active metabolites of phendimetrazine, which itself is inactive and behaves merely as a prodrug. Relative to phenmetrazine, pseudophenmetrazine is of fairly low potency, acting as a modest releasing agent of norepinephrine (EC50 = 514 nM), while its (+)-enantiomer is a weak releaser of dopamine (EC50 = 1,457 nM) whereas its (−)-enantiomer is a weak reuptake inhibitor of dopamine (Ki = 2,691 nM); together as a racemic mixture with the two enantiomers combined, pseudophenmetrazine behaves overall more as a dopamine reuptake inhibitor (Ki = 2,630 nM), possibly due to the (+)-enantiomer blocking the uptake of the (−)-enantiomer into dopaminergic neurons and thus preventing it from inducing dopamine release. Neither enantiomer has any significant effect on serotonin reuptake or release (both Ki = >10,000 nM and EC50 = >10,000 nM, respectively).
Selective serotonin reuptake inhibitors, or serotonin-specific re-uptake inhibitor (SSRIs), are a class of chemical compounds that have application as antidepressants and in the treatment of depression and other psychiatric disorders. SSRIs are therapeutically useful in the treatment of panic disorder (PD), posttraumatic stress disorder (PTSD), social anxiety disorder, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD), and anorexia. There is also clinical evidence of the value of SSRIs in the treatment of the symptoms of schizophrenia and their ability to prevent cardiovascular diseases.
Selective norepinephrine reuptake inhibitors (sNRIs) are a class of drugs that have been marketed as antidepressants and are used for various mental disorders, mainly depression and attention-deficit hyperactivity disorder (ADHD). The norepinephrine transporter (NET) serves as the fundamental mechanism for the inactivation of noradrenergic signaling because of the NET termination in the reuptake of norepinephrine (NE). The selectivity and mechanism of action for the NRI drugs remain mostly unresolved and, to date, only a limited number of NRI-selective inhibitors are available. The first commercially available selective NRI was the drug reboxetine (Edronax), developed as a first-line therapy for major depressive disorder. Atomoxetine (Strattera) is another potent and selective NRI which is also effective and well tolerated for the treatment of ADHD in adults; it may also be a new treatment option for adults with ADHD, particularly for those patients at risk of substance abuse.
