Dopaminergic

Main article: Dopamine

The chemical structure of the neurotransmitter dopamine

Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT₂), and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes which regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase (AAAD) or DOPA decarboxylase (DDC), monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Lastly, any endogenous or exogenous chemical substance which 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 opioids which enhance dopamine release indirectly in the reward pathways, and amphetamines, which enhance dopamine release directly by binding to, and inhibiting VMAT₂.

Supplements and drugs

A complete list of dopaminergic substances used as supplements and drugs includes:

• Dopamine (DA; Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc) itself, which is used in the treatment of severe hypotension, circulatory shock, and cardiac arrest as a vasopressor or antihypotensive agent.

• Precursors including L-phenylalanine (PHE), L-tyrosine (TYR), and L-DOPA (Levodopa; Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa, etc; also found in Mucuna pruriens (Velvet Bean)), which are all used as dietary supplements, and the latter of which is also used in the treatment of Parkinson's disease (PD).

• Cofactors including ferrous iron (Fe²⁺), tetrahydrobiopterin (THB, BH₄), vitamin B₃ (niacin, niacinamide) → NADPH, vitamin B₆ (pyridoxine, pyridoxamine, pyridoxal → pyridoxal phosphate (PLP), vitamin B₉ (folic acid) → tetrahydrofolic acid (THFA, H₄FA), vitamin C (ascorbic acid), and zinc (Zn²⁺), which are used as dietary supplements.

• Dopamine receptor agonists such as apomorphine (Apokyn, Uprima), bromocriptine (Parolodel), cabergoline (Dostinex), dihydrexidine (LS-186,899), dopamine (Intropin, Revivan), fenoldopam (Corlopam), piribedil (Trivastal), lisuride (Dopergin), pergolide (Permax), pramipexole (Mirapex), ropinirole (Requip), and rotigotine (Neupro), which are used in the treatment of Parkinson's disease (PD), restless legs syndrome (RLS), hyperprolactinemia (HPA), and sexual dysfunction (SD), as well as are being investigated in the treatment of depression and anxiety as antidepressants and anxiolytics, respectively.

• Dopamine receptor antagonists including typical antipsychotics such as chlorpromazine (Thorazine), fluphenazine (Prolixin), haloperidol (Haldol), loxapine (Loxitane), molindone (Moban), perphenazine (Trilafon), pimozide (Orap), thioridazine (Mellaril), thiothixene (Navane), and trifluoperazine (Stelazine), the atypical antipsychotics such as amisulpride (Solian), clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), sulpiride (Dogmatil), and ziprasidone (Geodon), and antiemetics like domperidone, metoclopramide (Reglan), and prochlorperazine (Compazine), among others, which are used in the treatment of schizophrenia (SCZ) and bipolar disorder (BD) as antipsychotics, and nausea and vomiting.

• Dopamine reuptake inhibitors (DRIs) or dopamine transporter (DAT) inhibitors such as methylphenidate (Ritalin, Focalin, Concerta), bupropion (Wellbutrin, Zyban), amineptine (Survector, Maneon, Directin), and nomifensine (Merital, Alival), as well as cocaine ("Coke", "Crack", etc), methylenedioxypyrovalerone (MDPV; "Sonic"), ketamine (K; Ketalar, Ketanest, Ketaset; "Special-K", "Kit Kat", etc), and phencyclidine (PCP; Sernyl; "Angel Dust", "Rocket Fuel", etc), among others, which are used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy as psychostimulants, obesity as anorectics, depression and anxiety as antidepressants and anxiolytics, respectively, drug addiction as anticraving agents, and sexual dysfunction, as well as illicit street drugs.

• Dopamine releasing agents (DRAs) such as amphetamine (Adderall, Dexedrine; "Speed"), lisdexamfetamine (Vyvanse), methamphetamine (Desoxyn; "Meth", "Crank", "Crystal", etc), methylenedioxymethamphetamine (MDMA; "Ecstasy", "E", "X", "XTC", etc), phenmetrazine (Preludin; "Prellies"), pemoline (Cylert), 4-methylaminorex (4-MAR; "Ice", "Euphoria", etc), and benzylpiperazine (BZP; "Bennies", "A2", "Sunrise", "Frenzy", etc), among many others, which, like DRIs, are used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy as psychostimulants, obesity as anorectics, depression and anxiety as antidepressants and anxiolytics, respectively, drug addiction as anticraving agents, and sexual dysfunction, as well as illicit street drugs.

• Dopamine activity enhancers such as BPAP and PPAP, which are currently only research chemicals, but are being investigated for clinical development in the treatment of a number of medical disorders.

• Vesicular monoamine transporter 2 (VMAT₂) inhibitors such as reserpine (Serpasil), tetrabenazine (Nitoman, Xenazine), and deserpidine (Harmonyl), which are used as sympatholytics or antihypertensives, and in the past as antipsychotics.

• Monoamine oxidase (MAO) inhibitors (MAOIs) including nonselective agents such as phenelzine (Nardil), tranylcypromine (Parnate), and isocarboxazid (Marplan), MAO_A selective agents like moclobemide (Aurorix, Manerix), and MAO_B selective agents such as selegiline (Eldepryl, Zelapar, Emsam), rasagiline (Azilect), and pargyline (Eutonyl), as well as the harmala alkaloids like harmine, harmaline, tetrahydroharmine, harmalol, harman, and norharman, which are found to varying degrees in Nicotiana tabacum (Tobacco; also cigarettes, cigars, chew, hookah, etc), Banisteriopsis caapi (Ayahausca, Caapi, Yage), Peganum harmala (Harmal, Syrian Rue), Passiflora incarnata (Passion Flower), and Tribulus terrestris (Puncture Vine), among others, which are used in the treatment of depression and anxiety as antidepressants and anxiolytics, respectively, in the treatment of Parkinson's disease (PD) and dementia, and for the recreational purpose of boosting the effects of certain drugs like phenethylamine (PEA) and psychedelics like dimethyltryptamine (DMT) via inhibiting their metabolism.

• Catechol O-methyl transferase (COMT) inhibitors such as entacapone (Comtan, Stalevo) and tolcapone (Tasmar), which are used in the treatment of Parkinson's disease (PD).

• Dopamine β-hydroxylase (DBH) inhibitors like disulfiram (Antabuse), which is used in the treatment of drug addiction as an anticraving agent.

• Phenylalanine hydroxylase (PAH) inhibitors like 3,4-dihydroxystyrene (DHS) which is currently only a research chemical with no suitable therapeutic indications, likely on account of the fact that such drugs would induce the potentially highly dangerous hyperphenylalaninemia (HPA) and/or phenylketonuria (PKU).

• Tyrosine hydroxylase (TH) inhibitors like metirosine (Demser), which is used in the treatment of pheochromocytoma (PCC) as a sympatholytic or antihypertensive agent.

• Aromatic L-amino acid decarboxylase (AAAD) or DOPA decarboxylase (DDC) inhibitors including benserazide (Prolopa, Madopar, etc), carbidopa (Lodosyn, Atamet, Parcopa, Sinemet, Stalevo, etc), and methyldopa (Aldomet, Aldoril, Dopamet, Dopegyt, etc), which are used in the treatment of Parkinson's disease (PD) in augmentation of L-DOPA ((Levodopa; Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa, etc)) to block the peripheral conversion of dopamine thereby inhibiting undesirable side effects, and as sympatholytic or antihypertensive agents.

• Others such as hyperforin and adhyperforin (both found in Hypericum perforatum (St. John's Wort (SJW))), L-theanine (found in Camellia sinensis (Tea Plant, also known as Black, White, Oolong, Pu-erh, or Green Tea)), and S-adenosyl-L-methionine (SAMe), which are all dietary supplements used mainly for the remedification of depression and anxiety as antidepressants and anxiolytics, respectively.