The following drugs have DRI action and have been or are used clinically specifically for this property:
amineptine,
dexmethylphenidate,
difemetorex,
fencamfamine,
lefetamine,
levophacetoperane,
medifoxamine,
mesocarb,
methylphenidate,
nomifensine,
pipradrol,
prolintane, and
pyrovalerone. The following drugs are or have been used clinically and possess only weak DRI action, which may or may not be clinically-relevant:
adrafinil,
armodafinil,
bupropion,
mazindol,
modafinil,
nefazodone,
sertraline, and
sibutramine. The following drugs are or have been clinically used but only coincidentally have DRI properties:
benzatropine,
diphenylpyraline,
etybenzatropine,
ketamine,
nefopam,
pethidine (meperidine), and
tripelennamine. The following are a selection of some particularly notably abused DRIs:
cocaine,
ketamine,
MDPV,
naphyrone, and
phencyclidine (PCP).
Amphetamines, including
amphetamine,
methamphetamine,
MDMA,
cathinone,
methcathinone,
mephedrone, and
methylone, are all DRIs as well, but are distinct in that they also behave, potentially more potently, as
dopamine releasing agents (DRAs) (due to
Yerkes–Dodson's law, 'more potently stimulated' may not equal more optimally functionally stimulated). There are very distinct differences 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 that 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 proven quite effective in managing excessive food consumption and regulating appetite in 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. ==Pharmacology==