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.
The dopamine transporter is a membrane-spanning protein coded for in humans by the SLC6A3 gene, that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dopamine into vesicles for storage and later release. Dopamine reuptake via DAT provides the primary mechanism through which dopamine is cleared from synapses, although there may be an exception in the prefrontal cortex, where evidence points to a possibly larger role of the norepinephrine transporter.
Phenmetrazine, sold under the brand name Preludin among others, is a stimulant drug first synthesized in 1952 and originally used as an appetite suppressant, but withdrawn from the market in the 1980s due to widespread misuse. It was initially replaced by its analogue phendimetrazine which functions as a prodrug to phenmetrazine, but now it is rarely prescribed, due to concerns of misuse and addiction. Chemically, phenmetrazine is a substituted amphetamine containing a morpholine ring or a substituted phenylmorpholine.
Phenylpiracetam, also known as fonturacetam and sold under the brand names Phenotropil, Actitropil, and Carphedon among others, is a stimulant and nootropic medication used in Russia and certain other Eastern European countries in the treatment of cerebrovascular deficiency, depression, apathy, and attention, and memory problems, among other indications. It is also used in Russian cosmonauts to improve physical, mental, and cognitive abilities. The drug is taken by mouth.
Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.
The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the SLC18A2 gene. SLC18A2 is an integral membrane protein that transports monoamines—particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine—from cellular cytosol into synaptic vesicles. In nigrostriatal pathway and mesolimbic pathway dopamine-releasing neurons, SLC18A2 function is also necessary for the vesicular release of the neurotransmitter GABA.
Phenyltropanes (PTs) were originally developed to reduce cocaine addiction and dependency. In general these compounds act as inhibitors of the plasmalemmal monoamine reuptake transporters. This research has spanned beyond the last couple decades, and has picked up its pace in recent times, creating numerous phenyltropanes as research into cocaine analogues garners interest to treat addiction.
Naphthylaminopropane, also known as naphthylisopropylamine (NIPA), is an experimental drug that was under investigation for the treatment of alcohol and stimulant addiction.
Mesocarb, sold under the brand name Sidnocarb or Sydnocarb and known by the developmental code name MLR-1017, is a psychostimulant medication which has been used in the treatment of psychiatric disorders and for a number of other indications in the Soviet Union and Russia. It is currently under development for the treatment of Parkinson's disease and sleep disorders. It is taken by mouth.
Norfenfluramine, or 3-trifluoromethylamphetamine, is a never-marketed drug of the amphetamine family and a major active metabolite of the appetite suppressants fenfluramine and benfluorex. The compound is a racemic mixture of two enantiomers with differing activities, dexnorfenfluramine and levonorfenfluramine.
In pharmacology, an indirect agonist or indirect-acting agonist is a substance that enhances the release or action of an endogenous neurotransmitter but has no specific agonist activity at the neurotransmitter receptor itself. Indirect agonists work through varying mechanisms to achieve their effects, including transporter blockade, induction of transmitter release, and inhibition of transmitter breakdown.
Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the TAAR1 gene.
2-Benzylpiperidine is a stimulant drug of the arylpiperidine family. It is similar in structure to certain other stimulants such as methylphenidate and desoxypipradrol. However, it is far less potent as a monoamine reuptake inhibitor in comparison. The drug is little used as a stimulant, with its main use being as a synthetic intermediate in the manufacture of other drugs.
A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitters and hence enhanced signaling by those neurotransmitters. The monoamine neurotransmitters include serotonin, norepinephrine, and dopamine; MRAs can induce the release of one or more of these neurotransmitters.
A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain.
RTI(-4229)-113 is a stimulant drug which acts as a potent and fully selective dopamine reuptake inhibitor (DRI). It has been suggested as a possible substitute drug for the treatment of cocaine addiction. "RTI-113 has properties that make it an ideal medication for cocaine abusers, such as an equivalent efficacy, a higher potency, and a longer duration of action as compared to cocaine." Replacing the methyl ester in RTI-31 with a phenyl ester makes the resultant RTI-113 fully DAT specific. RTI-113 is a particularly relevant phenyltropane cocaine analog that has been tested on squirrel monkeys. RTI-113 has also been tested against cocaine in self-administration studies for DAT occupancy by PET on awake rhesus monkeys. The efficacy of cocaine analogs to elicit self-administration is closely related to the rate at which they are administered. Slower onset of action analogs are less likely to function as positive reinforcers than analogues that have a faster rate of onset.
EPPTB, also known as RO5212773 or RO-5212773, is a drug developed by Hoffmann-La Roche which acts as a potent and selective antagonist or inverse agonist of the trace amine-associated receptor 1 (TAAR1). The drug was the first selective antagonist developed for the TAAR1. It is a potent agonist of the mouse and rat TAAR1, but is dramatically less potent as an agonist of the human TAAR1. EPPTB has been used in scientific research to demonstrate an important role for TAAR1 in regulation of dopaminergic signaling in the limbic system.
SoRI-9804 is a positive allosteric modulator of dopamine transporters. Unlike others in its series & traditional DRI ligands, it inhibits the release of dopamine in addition to inhibiting the reuptake of released dopamine back into the transporter.
RO5203648 is a trace amine-associated receptor 1 (TAAR1) partial agonist. It is a potent and highly selective partial agonist of both rodent and primate TAAR1. The drug suppresses the effects of psychostimulants like cocaine and methamphetamine. It also produces a variety of other behavioral effects, such as antidepressant-like, antipsychotic-like, and antiaddictive effects. Research with RO5203648 has led to interest in TAAR1 agonists for potential treatment of drug addiction. RO5203648 itself was not developed for potential medical use due to poor expected human pharmacokinetics.
Ethylnaphthylaminopropane is a monoamine releasing agent (MRA) of the amphetamine family that is related to naphthylaminopropane and methamnetamine. It acts specifically as a serotonin–norepinephrine–dopamine releasing agent (SNDRA). However, ENAP is unusual in being a partial releaser of serotonin and dopamine and a full releaser of norepinephrine.
