monoaminesdopamine

Monoamines are a class of neurotransmitters derived from aromatic amino acids, including dopamine, norepinephrine, epinephrine, serotonin, and histamine. Dopamine is a prominent monoamine neurotransmitter and a catecholamine concentrated in several brain circuits, notably the basal ganglia and limbic system, and also present in peripheral tissues.

Biosynthesis and clearance: Dopamine is synthesized from the amino acid tyrosine via tyrosine hydroxylase to L-DOPA, then decarboxylated to dopamine by DOPA decarboxylase. It is stored in synaptic vesicles by VMAT2, released by calcium-dependent exocytosis, and acts on dopamine receptors. After release, dopamine is removed from the synaptic cleft mainly by the dopamine transporter (DAT) reuptake, and is metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) to metabolites such as homovanillic acid.

Receptors and signaling: Dopamine binds to five receptor subtypes, divided into D1-like (D1, D5) and D2-like (D2, D3, D4) families, which modulate intracellular cAMP. Receptor distribution across brain regions underlies distinct pathways: the nigrostriatal pathway modulates motor control; the mesolimbic and mesocortical pathways regulate reward, motivation, and executive function; the tuberoinfundibular pathway influences prolactin release.

Functions and clinical relevance: Dopamine influences movement, reward learning, motivation, mood, and cognition. Dysregulation is implicated in Parkinson's disease, schizophrenia, ADHD, and substance use disorders. Therapeutic strategies include L-DOPA and other dopaminergic medications for Parkinson's disease, and dopamine receptor antagonists as antipsychotics for psychiatric conditions. Peripheral dopamine contributes to kidney function and vascular tone in certain contexts, but central effects predominate in clinical considerations.