A drug that leaves blocks the uptake mechanism in a neural receptor. This leaves dopamine on the receptor, increasing the effects of that neurotransmitter. In this case, this effect can create a short, intense high.

An example of this kind of drug is cocaine.

While dopamine reuptake inhibitors can produce a sharp high, such as that of cocaine, they can also have theraputic effects when delivered to the bloodstream over time or by continuous administration resulting in depolarization block. Examples of commonly prescribed medications that exert their effect through inhibition of the dopamine reuptake transporter include Ritalin and Wellbutrin, both of which are indicated in the treatment of ADHD. Wellbutrin is also used to treat depression, and under the brand name Zyban, to aid in the cessation of smoking. Because of Ritalin's similarity to cocaine, it has a high abuse potential, and is therefore classified as a controlled substance in the United States. Wellbutrin has yet to see politically significant abuse as a street drug, and so as yet is not scheduled as a controlled substance.

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