There are five established biogenic amine neurotransmitters: the three catecholamines dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) and histamine and serotonin In terms of synthesis, packaging, release, and degradation, the amine neurotransmitters fall somewhere between the properties of the other small-molecule neurotransmitters and those of the neuropeptides. All the catecholamines are derived from a common precursor, the amino acid tyrosine. The first step in catecholamine synthesis is catalysed by tyrosine hydroxylase in a reaction requiring oxygen as a co[1]substrate and tetrahydrobiopterin as a cofactor to synthesize dihydroxyphenylalanine (DOPA). Because tyrosine hydroxylase is rate-limiting for the synthesis of all three transmitters, its presence is a valuable criterion for identifying catecholaminergic neurons. Vanillylmandelic acid (VMA) and other catecholamine metabolites are typically elevated in patients with catecholamine-secreting tumours (eg, neuroblastoma, pheochromocytoma, and other neural crest tumours). VMA levels may also be useful in monitoring patients who have been treated as a result of 1 of the above[1]mentioned tumours. Pheochromocytoma is a rare, though potentially lethal, tumour of chromaffin cells of the adrenal medulla that produces episodes of hypertension with palpitations, severe headaches, and sweating ("spells"). Patients with pheochromocytoma may also be asymptomatic and present with sustained hypertension or an incidentally discovered adrenal mass. Pheochromocytomas and other tumours derived from neural crest cells (eg, paragangliomas and neuroblastomas) secrete catecholamines (epinephrine, norepinephrine, and dopamine). Metanephrine and normetanephrine (collectively referred to as metanephrines) are the 3-methoxy metabolites of epinephrine and norepinephrine, respectively. The metanephrines are stable metabolites and are cosecreted directly with catecholamines by pheochromocytomas and other neural crest tumours. This results in sustained elevations in plasma free metanephrine levels, making them more sensitive and specific than plasma catecholamines in the identification of pheochromocytoma patients. Metanephrine and normetanephrine are both further metabolized to conjugated metanephrines and vanillylmandelic acid neurotransmitters from presynaptic neural cells to postsynaptic receptors. Alterations in the levels of specific neurotransmitters have been observed in various neurological disorders, including Parkinson disease, schizophrenia, depression, and Alzheimer disease.