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Other names | RDS3-094 |
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Formula | C24H32F2N2OS |
Molar mass | 434.59 g·mol−1 |
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RDS03-94, or RDS3-094, is an atypical dopamine reuptake inhibitor that was derived from the wakefulness-promoting agent modafinil. [1] [2] [3] [4]
It has substantially higher affinity and potency in terms of dopamine transporter (DAT) inhibition than modafinil (Ki = 39.4 nM vs. 8,160 nM) whilst retaining the atypical DAT blocker profile of modafinil. [1] [2] However, RDS03-94 also has high affinity for the sigma σ1 receptor (Ki = 2.19 nM). [2]
RDS03-94 shows some reversal of tetrabenazine-induced motivational deficits in animals and hence may have the capacity to produce pro-motivational effects. [5] [6] However, it appears to be less effective than certain other related agents, like JJC8-088. [6] [5]
RDS03-94 is under development for the treatment of psychostimulant use disorder. [1] The drug was first described in the scientific literature in 2020. [1] [2]
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.
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Flmodafinil, also known as bisfluoromodafinil and lauflumide, is a wakefulness-promoting agent related to modafinil which has been developed for treatment of a variety of different medical conditions. These include chronic fatigue syndrome, idiopathic hypersomnia, narcolepsy, attention deficit hyperactivity disorder (ADHD), and Alzheimer's disease. Aside its development as a potential pharmaceutical drug, flmodafinil is sold online and used non-medically as a nootropic.
1-(3-Chlorophenyl)-4-(2-phenylethyl)piperazine (3C-PEP) is a designer drug of the piperazine class of chemical substances. 3C-PEP is related to meta-cholorophenylpiperazine (mCPP) and phenethylamine that can be thought of as mCPP having a phenylethyl group attached to the nitrogen atom at its 4-position. It was first described in 1994 in a patent disclosing a series of piperazine compounds as sigma receptor ligands. Later, it was discovered to be a highly potent dopamine reuptake inhibitor.
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JJC8-091 is an atypical dopamine reuptake inhibitor (DRI) that was derived from modafinil. It is a lead compound for potential treatment of psychostimulant use disorder (PSUD) and is under development by Encepheal Therapeutics for use as a pharmaceutical drug.
JJC8-089 is a dopamine reuptake inhibitor (DRI) that was derived from modafinil and is related to JJC8-016, JJC8-088, and JJC8-091. Its affinity (Ki) for the dopamine transporter (DAT) is 37.8 nM, for the norepinephrine transporter (NET) is 11,820 nM, for the serotonin transporter (SERT) is 6,800 nM, and for the sigma σ1 receptor is 2.24 nM. It also has significant affinity for several dopamine receptors. JJC8-089 has substantially higher affinity for the DAT than modafinil. The drug shows pro-motivational effects in animals. It was first described in the scientific literature by 2016.
More recently, by introducing the 2,6-dimethyl substitution on the piperazine ring, some improvement in drug-like properties was realized with RDS03-94 [29]. Nevertheless, the piperazine ring remained a metabolically labile functional group and hence a new series of analogues in which it was replaced with an amino-piperidine function was prepared [30]. These new analogues demonstrated superior metabolic stability and are currently being evaluated in rodent models of [psychostimulant use disorder (PSUD)]. In addition, novel heterocyclic-based analogues that may also be promising new leads for PSUD therapeutics have recently been reported [31,32].