Kinetic Modeling of Dopamine Transport Protein Inhibition by Indole Based Modafinil Analogs Using Rotating Disk Voltammetry

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Description

Dopamine neurons, which synthesize and release the neurotransmitter dopamine, create the reward circuit in our brains which allows us to feel pleasure and motivates us to repeat pleasurable behaviors. For example, eating a piece of chocolate causes the release of dopamine and reinforces the pleasure associated with chocolate consumption. Other functions of dopamine are regulation of sleep and motor movement.

Presynaptic dopaminergic neurons release dopamine which diffuses across the synaptic cleft and binds to receptors on the receiving (postsynaptic) neuron. The signal is terminated when dopamine is transported back into the pre-synaptic cell that released it by a protein called the dopamine transporter. The dopamine transporter is the target of the therapeutics modafinil (a narcolepsy medication) and Ritalin (an ADHD medication) and the drugs of abuse cocaine and amphetamines. By inhibiting the dopamine transporter, these drugs slow down the reuptake of dopamine, increasing the dopamine signal. Modafinil specifically does this to promote wakefulness in people with sleep disorders. The goal of our project is to use small molecules with structures similar to modafinil (called structural analogs) to see how they affect the rate of reuptake of dopamine. The collected data is analyzed using kinetic models to learn about the dopamine transporter protein.

Advisor

Dr. Cynthia Ochsner, Chemistry

Publication Date

2023

Keywords

chemistry, dopamine

Kinetic Modeling of Dopamine Transport Protein Inhibition by Indole Based Modafinil Analogs Using Rotating Disk Voltammetry
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