Dopamine

Dopamine is a sympathomimetic and is "one of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (dopamine receptors) mediate its action."

Dopamine regulates the secretion of prolactin from the anterior pituitary gland. Dopamine is released from specialised neurons of the arcuate nucleus of the hypothalamus into the blood vessels of the median eminence, which transport the dopamine to the pituitary gland where it inhibits prolactin secretion from lactotroph cells.

Various drugs mediate its metabolism, and it is given directly as a vasopressor to raise blood pressure and a positive inotropic agent to increase cardiac output.

Physiology

Dopamine plasma membrane transport proteins are "sodium chloride-dependent neurotransmitter symporters located primarily on the plasma membrane of dopaminergic neurons. They remove dopamine from the extracellular space by high affinity reuptake into presynaptic terminals and are the target of dopamine uptake inhibitors."

Dopamine pathways

The dopaminergic systems include:

• Tuberoinfundibular dopaminergic system: "tuberoinfundibular DA cells that projects from the arcuate and periventricular nuclei to the intermediate lobe of the hypophysis and the median eminence." Dopamine released here inhibits prolactin secretion.
• Nigrostriatal dopaminergic system - the neostriatum (caudate nucleus and putamen). Important in movement disorders.
• Mesocortical dopaminergic system - the limbic cortex (medial prefrontal, cingulate and entorhinal areas) which is important in schizophrenia.
• Mesolimbic dopaminergic systems - limbic system (septum, olfactory tubercle, nucleus accumbens septi, amygdala complex, and piriform cortex) that affects reward and reinforcement.

Dopamine receptors

D₁-like receptors

These receptors stimulate adenylate cyclase.

D1 receptors

D5 receptors

D₂-like receptors

These receptors inhibit adenylate cyclase.

Dopamine D2 receptors

Agonists, such as metoclopramide, are used as antiemetics.

Antagonists, such as risperidone and haloperidol, are used to treat schizophrenia.

Blockade of the D2 receptors, which may be predisposed by genetic polymorphisms of the allele, may cause neuroleptic malignant syndrome.

D3 receptors

Agonists of D3, especially nonergot agonists such as pramipexole and ropinirole, may be used to treat Parkinonism and restless legs syndrome.

D4 receptors

Dopamine in disease

Movement disorders

Neuroleptic malignant syndrome

Blockade of the D2 receptors, which may be predisposed by genetic polymorphisms of the allele, may cause neuroleptic malignant syndrome.

Benign essential blepharospasm

Benign essential blepharospasm may be associated with polymorphism in the dopamine receptor D5.

Psychiatric disorders

Attention deficit hyperactivity disorder

ADHD may result from reduced inhibitory dopamine transmission in the midbrain. This may be due to an increase in dopamine plasma membrane transport protein density which may remove dopamine from the synapse too quickly.

Drug abuse

The rewarding effects of amphetamines and cocaine are due to dopamine activity. Cocaine increases monoamine levels by binding to serotonin (5-HT), norepinephrine (NE), and dopamine (DA) catecholamine plasma membrane transport proteins. This blockade prevents the reuptake of neurotransmitters, thus increasing the amount available at the synapse to bind to the post synaptic cell. In contrast to amphetamine, a similar psychomotor stimulant, cocaine is a dopamine uptake inhibitor and does not stimulate DA release. Cocaine's rewarding effects come primarily from increased activity in the mesolimbic dopamine pathway.

Novelty Seeking Personality Trait

Novelty seeing personality trait may be related to polymorphisms in the dopamine receptor D4 that affects dopamine activity in the tuberoinfundibular dopaminergic system.

Schizophrenia

The dopamine hypothesis proposes that schizophrenia is in part due to excessive dopaminergic activity.

Clinical pharmacology

Dopamine

Parenteral dopamine is used to raise blood pressure and cardiac output in acute decompensated heart failure, acute hypotension, low cardiac output, and acute renal disease. It also is used to correct sinus bradycardia.

Dopamine agonists

Dopamine agonists are "drugs that bind to and activate dopamine receptors."

Agonists of dopamine receptor D3, especially nonergot agonists such as pramipexole and ropinirole, may be used to treat Parkinonism and restless legs syndrome.

Dopamine antagonists

Dopamine antagonists are "drugs that bind to but do not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (antipsychotic agents) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as antiemetics, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with neuroleptic malignant syndrome."

Dopamine uptake inhibitors

Dopamine uptake inhibitors are "drugs that block the transport of dopamine into axon terminals or into storage vesicles within terminals. Most of the adrenergic uptake inhibitors also inhibit dopamine uptake." Dopamine uptake inhibitors affect dopamine plasma membrane transport proteins.

Examples include amphetamines, bupropion, cocaine, and methylphenidate. Some of these drugs are also adrenergic uptake inhibitors.

Venlafaxine, depending on the dose, has selective reuptake inhibition activities. Low doses inhibit serotonin uptake. Higher doses inhibit norepinephrine reuptake, while the highest doses block dopamine reuptake.