Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter.
Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and that Biosynthesis or contain dopamine and with dopamine receptors in them may also be labeled as dopaminergic. that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well.
Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that release dopamine or express dopamine receptors) can also be said to have dopaminergic effects, two prominent examples being , which enhance dopamine release indirectly in the , and some substituted amphetamines, which enhance dopamine release directly by binding to and inhibiting VMAT2.
Dopaminergic agents
Dopamine precursors
Dopamine precursors including
L-phenylalanine and
L-tyrosine are used as dietary supplements.
L-DOPA (Levodopa), another precursor, is used in the treatment of Parkinson's disease.
of levodopa, including
melevodopa,
etilevodopa,
foslevodopa, and XP-21279 also exist. They are inactive themselves but are converted into dopamine and hence act as non-selective dopamine receptor agonists.
Dopamine receptor ligands
Dopamine receptor agonists
Dopamine receptor agonists can be divided into non-selective dopamine receptor agonists, D
1-like receptor agonists, and D
2-like receptor agonists.
Non-selective dopamine receptor agonists include dopamine, deoxyepinephrine (epinine), dinoxyline, and dopexamine. They are mostly peripherally selective drugs, are often also adrenergic receptor agonists, and are used to treat certain cardiovascular conditions.
D2-like receptor agonists include the bromocriptine, cabergoline, dihydroergocryptine, ergoloid, lisuride, metergoline, pergolide, quinagolide, and terguride; the morphine analogue apomorphine; and the structurally distinct agents piribedil, pramipexole, ropinirole, rotigotine, and talipexole. Some of these agents also have weak affinity for the D1-like receptors. They are used to treat Parkinson's disease, restless legs syndrome, hyperprolactinemia, , acromegaly, erectile dysfunction, and for lactation suppression. They are also being studied in the treatment of depression and are sometimes used in the treatment of disorders of diminished motivation like apathy, abulia, and akinetic mutism.
D1-like receptor agonists include 6-Br-APB, A-68930, A-77636, A-86929, adrogolide, dihydrexidine, dinapsoline, doxanthrine, fenoldopam, razpipadon, SKF-81,297, SKF-82,958, SKF-89,145, tavapadon, and trepipam. They have been researched for and are under development for the treatment of Parkinson's disease and dementia-related apathy. Peripherally selective D1-like receptor agonists like fenoldopam are used to treat hypertensive crisis.
Dopamine receptor positive allosteric modulators
Positive allosteric modulators of the dopamine D
1 receptor like
mevidalen and
glovadalen are under development for the treatment of Lewy body disease and Parkinson's disease.
Dopamine receptor antagonists
Dopamine receptor antagonists including typical antipsychotics such as
chlorpromazine (Thorazine),
fluphenazine,
haloperidol (Haldol),
loxapine,
molindone,
perphenazine,
pimozide,
thioridazine,
thiothixene, and
trifluoperazine, the atypical antipsychotics such as
amisulpride,
clozapine,
olanzapine,
quetiapine (Seroquel),
risperidone (Risperdal),
sulpiride, and
ziprasidone, and
like
domperidone,
metoclopramide, and
prochlorperazine, among others, which are used in the treatment of
schizophrenia and
bipolar disorder as
, and
nausea and
vomiting.
Dopamine receptor antagonists can be divided into D1-like receptor antagonists and D2-like receptor antagonists. Ecopipam is an example of a D1-like receptor antagonist.
At low doses, dopamine D2 and D3 receptor antagonists can preferentially block presynaptic dopamine D2 and D3 and thereby increase dopamine levels and enhance dopaminergic neurotransmission.
Dopamine receptor negative allosteric modulators
Negative allosteric modulators of the dopamine receptors, such as SB269652, have been identified and are being researched.
Dopamine transporter modulators and related
Dopamine reuptake inhibitors
Dopamine reuptake inhibitors (DRIs) or dopamine transporter (DAT) inhibitors such as
methylphenidate (Ritalin),
amineptine,
nomifensine,
cocaine,
bupropion,
modafinil,
armodafinil,
phenylpiracetam,
mesocarb, and
vanoxerine, among others. They are used in the treatment of attention-deficit hyperactivity disorder (ADHD) as
,
narcolepsy as wakefulness-promoting agents,
obesity and binge eating disorder as appetite suppressants, depression as
, and fatigue as pro-motivational agents. They are also used as illicit
street drug and recreational drugs due to their potentially
euphoriant and psychostimulant effects.
Dopamine releasing agents
Releasing agent (DRAs) such as
phenethylamine,
amphetamine,
lisdexamfetamine (Vyvanse),
methamphetamine, methylenedioxymethamphetamine (MDMA),
phenmetrazine,
pemoline, 4-methylaminorex (4-MAR),
phentermine, and
benzylpiperazine, among many others, which, like DRIs, are used in the treatment of attention-deficit hyperactivity disorder (ADHD) and
narcolepsy as
,
obesity as
, depression and
anxiety as
and
respectively,
drug addiction as anticraving agents, and sexual dysfunction as
. Many of these compounds are also illicit
street drug or recreational drugs.
Dopaminergic activity enhancers
Dopaminergic activity enhancers such as the prescription drug
selegiline (deprenyl) and the research chemicals BPAP and PPAP enhance the
action potential-mediated release of dopamine.
This is in contrast to dopamine releasing agents like amphetamine, which induce the uncontrolled release of dopamine regardless of electrical stimulation.
The effects of the activity enhancers may be mediated by
intracellular TAAR1
agonist coupled with uptake into monoaminergic neurons by monoamine transporters.
Dopaminergic activity enhancers are of interest in the potential treatment of a number of
, such as depression and Parkinson's disease. To date, only
phenylethylamine,
tryptamine, and
tyramine have been identified as endogenous activity enhancers.
Dopamine depleting agents
Vesicular monoamine transporter 2 (VMAT
2) inhibitors such as
reserpine,
tetrabenazine,
valbenazine, and
deutetrabenazine act as dopamine depleting agents and are used as
or
, to treat tardive dyskinesia, and in the past as
. They have been associated with side effects including depression,
apathy, fatigue,
amotivation, and
suicidality.
Dopamine metabolism modulators
Monoamine oxidase inhibitors
Monoamine oxidase (MAO) inhibitors (MAOIs) including non-selective agents such as
phenelzine,
tranylcypromine,
isocarboxazid, and
pargyline,
MAO-A selective agents like
moclobemide and
clorgyline, and
MAO-B selective agents such as
selegiline and
rasagiline, as well as the
like
harmine,
harmaline, tetrahydroharmine,
harmalol,
harmala alkaloid, and
norharman, which are found to varying degrees in
Nicotiana tabacum (tobacco),
Banisteriopsis caapi (ayahuasca, yage),
Peganum harmala (Harmal, Syrian Rue),
Passiflora incarnata (Passion Flower), and
Tribulus terrestris, among others, which are used in the treatment of depression and
anxiety as
and
, respectively, in the treatment of Parkinson's disease and
dementia, and for the recreational purpose of boosting the effects of certain
like
phenethylamine (PEA) and
psychedelic drug like dimethyltryptamine (DMT) via inhibiting their
metabolism.
Catechol O-methyltransferase inhibitors
Catechol
O-methyl transferase (COMT)
COMT inhibitor such as
entacapone,
opicapone, and
tolcapone, which are used in the treatment of Parkinson's disease. Entacapone and opicapone are peripherally selective, but tolcapone significantly crosses the blood–brain barrier. Tolcapone is under study for potential treatment of certain psychiatric disorders such as obsessive–compulsive disorder and
schizophrenia.
Aromatic L-amino acid decarboxylase inhibitors
Aromatic L-amino acid decarboxylase (AAAD) or DOPA decarboxylase inhibitors including
benserazide,
carbidopa, and
methyldopa, which are used in the treatment of Parkinson's disease in augmentation of
L-DOPA to block the
peripheral conversion of
dopamine, thereby inhibiting undesirable
adverse effect, and as
sympatholytic or
antihypertensive agents.
Dopamine β-hydroxylase inhibitors
Dopamine β-hydroxylase inhibitors like
disulfiram (Antabuse), which can be used in the treatment of addiction to cocaine and similar dopaminergic drugs as a deterrent drug. The excess dopamine resulting from inhibition of the dopamine β-hydroxylase enzyme increases unpleasant symptoms such as anxiety, higher blood pressure, and restlessness. Disulfiram is not an anticraving agent, because it does not decrease craving for drugs. Instead, positive punishment from its unpleasant effects deters drug consumption.
Other dopamine β-hydroxylase inhibitors include the centrally active
nepicastat and the peripherally selective
etamicastat and
zamicastat.
Other enzyme inhibitors
Phenylalanine hydroxylase inhibitors like 3,4-dihydroxystyrene), which is currently only a research chemical with no suitable therapeutic indications, likely because such drugs would induce the potentially highly dangerous hyperphenylalaninemia or
phenylketonuria.
Tyrosine hydroxylase inhibitors like metirosine, which is used in the treatment of pheochromocytoma as a sympatholytic or antihypertensive agent.
Dopaminergic neurotoxins
Dopaminergic neurotoxins like 6-hydroxydopamine (6-OHDA) and
MPTP are used in scientific research to
lesion the dopamine system and study the biological role of dopamine.
Miscellaneous agents
Adamantane derivatives
Amantadine has dopaminergic effects through uncertain mechanisms of action.
It is structurally related to other
like
bromantane and
rimantadine, which also have dopaminergic actions.
Bromantane can upregulate tyrosine hydroxylase (TH) and thereby increase dopamine production and this might be involved in its dopaminergic effects.
Amantadine can upregulate TH similarly, but as with bromantane, it is unclear whether this is involved in or responsible for its dopaminergic actions.
Amantadine is used in the treatment of Parkinson's disease, levodopa-induced dyskinesia, and fatigue in multiple sclerosis. It has also been used in the treatment of disorders of consciousness, disorders of diminished motivation, and
brain injury. The drug is being studied in the treatment of depression and attention deficit hyperactivity disorder (ADHD) as well.
Diphenylpiperidines
4,4-Diphenylpiperidines including
budipine and
prodipine are effective in the treatment of Parkinson's disease.
Their mechanism of action is unknown but they act as indirect dopaminergic agents.
They have distinct effects from other antiparkinsonian agents and dopaminergic drugs.
Other miscellaneous agents
Aspirin upregulates tyrosine hydroxylase and increases dopamine production.
Others such as hyperforin and adhyperforin (both found in Hypericum perforatum St. John's Wort), L-theanine (found in Camellia sinensis, the tea plant), and S-adenosyl-L-methionine (SAMe).
See also
