The pathways that are used to synthesise from tyrosine, the biogenic amine neuromediators levodopa, dopamine, adrenaline, noradrenaline and from tryptophan the neuromediator serotonin are useful to understand in the context of a number of diseases including Parkinson's disease and pheochromocytoma. The ultimate metabolites homovanillic acid, vanillylmandelic acid and hydroxyindoleacetic acid are often evaluated in the urine in the work up of some of these diseases. They may also be evaluated in disorders of metabolism causing monoamine disorder. Inherited monoamine disorders have a wide impact, not just on individuals but also society, as they can modulate addictive behaviour and a large number of disease presentations. Acquired disorders affecting monoamines, include those related to substance abuse, changes in neuro-endocrine balance brought on by drugs and neuroendocrine tumours.

Genetic disorders

These include:

• The multiple associations of the SLC6A3 gene with:
  • Infantile onset parkinsonism
  • Addiction
  • Parkinsonism
  • Schizophrenia
  • Bipolar disorder
  • Tourette syndrome
  • Attention deficit hyperactivity disorder
• The dopa-responsive dystonias.
• Deficiency of aromatic amino acid decarboxylase (AADC gene defect) leads to a chronic and progressive neurological disorder with^[2]:
  • Development delay
  • Dyskinesias
  • Oculogyric crisis
  • Vegetative symptoms

Significance of decreased lumbar CSF levels of HVA and 5-HIAA in Alzheimer's disease.

The monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxy-phenylglycol (HMPG) were determined in lumbar cerebrospinal fluid (CSF) of 123 patients with Alzheimer's disease (AD) and 57 healthy controls. Despite CSF sampling under strictly standardized conditions, a wide variability in values among both patients and controls was found, as well as fluctuations in repeated samples from individual patients. This suggests that several unknown factors influence the lumbar CSF levels of monoamine metabolites. The AD group showed significantly lower mean levels of HVA (p less than 0.0001) and 5-HIAA (p less than 0.0001) than the control group. A relation between severity of disease and HVA was also found. The widespread neurotransmitter disturbance in AD, together with the nonspecificity of reduced lumbar HVA and 5-HIAA levels, suggests that the changes are nonspecific, secondary to the cerebral degeneration in AD.

Vanylglycol (MHPG) is a O-methylated metabolite of normetanephrine. MHPG is formed by catechol-O-methyltransferase (COMT) from norepinephrine. Catecholamines play an important role in platelet activation and aggregation, epinephrine being the most potent one. Catecholamines are substantially increased during stress, exercise or smoking and could result in clinically important platelet activation if their action was not rapidly regulated. MHPG is found normally in urine, in plasma and cerebrospinal fluid. Alcohol consumption increases the level of HMPG in urine and CSF. Alcohol dehydrogenase has been shown to act on norepinephrine and produce HMPG