in the mode of action between dopamine releasers/substrates & dopamine re-uptake inhibitors; the former are functionally entropy-driven (i.e. relating to hydrophobicity) and the latter are enthalpy-driven (i.e. relating conformational change). Reuptake inhibitors such as cocaine induce hyperpolarization of cloned human DAT upon oocytes that are naturally found on neurons, whereas releasing agents induce de-polarization of the neuron membrane. The wakefulness-promoting agent modafinil and its analogues (e.g., adrafinil, armodafinil) have been approved to treat narcolepsy and shift work sleep disorder. These act as weak (micromolar) DRIs, but this effect does not correlate with wakefulness-promoting effects, suggesting the effect is too weak to be of clinical significance. The conclusion is these drugs promote wakefulness via some other mechanism. DRIs have been explored as potential antiaddictive agents in the context of replacement therapy strategies, analogous to nicotine replacement for treating tobacco addiction and methadone replacement in the case of opioid addiction. DRIs have been explored as treatment for cocaine addiction, and have shown to alleviate cravings and self-administration. Monoamine reuptake inhibitors, including DRIs, have shown effectiveness as therapy for excessive food intake and appetite control for obese patients. Though such pharmacotherapy is still available, the majority of stimulant anorectics marketed for this purpose have been withdrawn or discontinued due to adverse side effects such as hypertension, valvulopathy, and drug dependence. List of DRIs Only DRIs which are selective for the DAT over the other monoamine transporters (MATs) are listed below. For a list of DRIs that act at multiple MATs, see other monoamine reuptake inhibitor pages such as NDRI and SNDRI. Selective dopamine reuptake inhibitors 4-Hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-methylphenyl ketone Altropane (O-587) Amfonelic acid (WIN 25978) Amineptine (has a reasonable degree of selectivity for dopamine over norepinephrine reuptake inhibition) BTCP (GK-13), same acronym as for breakthrough cancer pain. 3C-PEP DBL-583 Difluoropine (O-620) GBR-12783 GBR-12935 GBR-13069 GBR-13098 GYKI-52895 Iometopane (β-CIT, RTI-55) Ethylphenidate (more selective for DA vs NE reuptake inhibition compared to methylphenidate, but still has a marked effect on both) Modafinil (relatively weak but very selective for the dopamine transporter, with little to no effect on the norepinephrine or serotonin transporters) Armodafinil (R-enantiomer of modafinil; somewhat more potent at inhibiting DAT than racemic modafinil, with equally negligible action on NET and SERT) RTI-229 Vanoxerine (GBR-12909) DRIs with substantial activity at other sites Adrafinil (weak, possibly stressful on liver) Amantadine (also a weak NMDA receptor antagonist) Benztropine (also muscarinic antagonist) Bupropion (also a more potent NRI