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Pharmacology Dopamine itself is a useful drug, in injectable form, but there are many other important drugs that exert their effects by acting on dopamine systems in various parts of the brain or body. Some are used for medical or recreational purposes, but neurochemists have also developed a variety of research drugs, some of which bind with high affinity to specific types of dopamine receptors and agonize or antagonize their effects, and many that affect other aspects of dopamine physiology.<ref>{{#invoke:citation/CS1|citation |CitationClass=book }}</ref>


L-DOPA or Levodopa—the two names are equivalent—is the metabolic precursor of dopamine: it is converted to dopamine in the brain and various parts of the body by the enzyme DOPA decarboxylase.<ref name=Musacchio/> Because L-DOPA, unlike dopamine itself, is capable of crossing the blood-brain barrier, it is widely used to treat Parkinson's disease, as well as dopa-responsive dystonias.<ref name="Nice-pharma">{{#invoke:citation/CS1|citation |CitationClass=book }}</ref> It is often co-administered with an inhibitor of peripheral decarboxylation such as carbidopa or benserazide, to reduce the amount converted to dopamine in the periphery and thereby increase the amount of L-DOPA that enters the brain.<ref name="Nice-pharma"/> When L-DOPA is administered regularly over a long time period, a variety of unpleasant side effects such as dyskinesia often begin to appear; even so, it is considered the best available long-term treatment option for most cases of Parkinson's disease.<ref name="Nice-pharma"/>


Diagram describes the mechanisms by which cocaine and amphetamines reduce dopamine transporter activity.
Cocaine increases dopamine levels by blocking dopamine transporters (DAT), which transport dopamine back into a synaptic terminal after it has been emitted.

Cocaine, substituted amphetamines (including methamphetamine), Adderall, methylphenidate (marketed as Ritalin or Concerta), MDMA (ecstasy) and other so-called psychostimulants exert their effects primarily or partly by increasing dopamine levels in the brain by a variety of mechanisms.<ref name=Ghodse/> Cocaine and methylphenidate are dopamine transporter blockers: they non-competitively inhibit dopamine reuptake, resulting in increased dopamine concentrations in the synaptic cleft.<ref name=Heal>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name=Freye>{{#invoke:citation/CS1|citation |CitationClass=book }}</ref> Like cocaine, substituted amphetamines increase the concentration of dopamine in the synaptic cleft, but by a different mechanism, involving complex intracellular effects.<ref name=Miller>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> MDMA also increases dopamine levels by a complex combination of mechanisms.<ref name=Freye2>{{#invoke:citation/CS1|citation |CitationClass=book }}</ref>

The effects of psychostimulants include increases in heart rate, body temperature, and sweating; improvements in alertness, attention, and endurance; increases in pleasure produced by rewarding events; but at higher doses agitation, anxiety, or even loss of contact with reality.<ref name=Ghodse>{{#invoke:citation/CS1|citation |CitationClass=book }}</ref> Drugs in this group can have a high addiction potential, due to their activating effects on the dopamine-mediated reward system in the brain.<ref name=Ghodse/> However some can also be useful, at lower doses, for treating attention deficit hyperactivity disorder (ADHD).<ref name=Kimko/> An important differentiating factor is the onset and duration of action.<ref name=Ghodse/> Cocaine can take effect in seconds if it is injected or inhaled in free-base form; the effects last from 5 to 90 minutes.<ref name=Zimmerman>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> This rapid and brief action gives it high addiction potential.<ref name=Ghodse/> Methylphenidate taken in pill form, in contrast, can take two hours to reach peak levels in the bloodstream, and depending on formulation the effects can last for up to 12 hours.<ref name=Kimko>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> These slow and sustained actions reduce the addiction potential and make it more useful for treating ADHD.<ref name=Kimko/>

Antipsychotic drugs

{{#invoke:main|main}} A range of drugs that reduce dopamine activity have been found useful in the treatment of schizophrenia and other disorders that produce psychosis.<ref name=Healy>{{#invoke:citation/CS1|citation |CitationClass=book }}</ref> These antipsychotic drugs are also sometimes known as neuroleptics or "major tranquilizers", in contrast to "minor tranquilizers" such as Valium that are used to treat anxiety or sleep disorders.<ref name=Healy/> The most prominent effect of these drugs is to reduce the activity of dopamine systems, mainly by antagonizing D2 receptors.<ref name = Brunton>{{#invoke:citation/CS1|citation |CitationClass=book }}</ref> Antipsychotic drugs have a broadly suppressive effect on most types of active behavior, and particularly reduce the delusional and agitated behavior characteristic of overt psychosis.<ref name=Brunton/> The introduction of the first widely used antipsychotic drug, chlorpromazine (Thorazine), in the 1950s, led to the release of many schizophrenia patients from institutions in the years that followed.<ref name=Healy/>

Even so, the widespread use of antipsychotic drugs has long been controversial.<ref name=James>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> There are several reasons for this. First, antipsychotic drugs are perceived as very aversive by people who have to take them, because they produce a general dullness of thought and suppress the ability to experience pleasure.<ref name=Lambert>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Second, it is difficult to show that they act specifically against psychotic behaviors rather than merely suppressing all types of active behavior.<ref name=James/> Third, they can produce a range of serious side effects, including weight gain, diabetes, fatigue, sexual dysfunction, hormonal changes, and a type of movement disorder known as tardive dyskinesia.<ref name=Muench>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Some of these side effects may continue long after the cessation of drug use, or even permanently.<ref name=Muench/>

The first drugs introduced specifically for the treatment of psychosis all had strong direct effects on dopamine receptors of the D2 class.<ref name=Brunton/> Drugs of this type are known as typical antipsychotics.<ref name=Healy/> In the following decades other types of antipsychotic drugs with fewer serious side-effects were developed, known as atypical antipsychotics.<ref name=Healy/> Many of these newer drugs do not act directly on dopamine receptors, but detailed investigation has shown that almost all of them produce alterations in dopamine activity indirectly.<ref name=Horacek>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> There remains substantial dispute, however, about how much of an improvement in the patient experience these drugs produce.<ref name=James/>

Dopamine sections
Intro  Structure  Biochemistry  Functions  Medical uses  Pharmacology  Diseases and disorders  Comparative biology and evolution  History and development  See also   References   

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