• Belong to a family of membrane-bound guanine nucleotide-binding protein-coupled receptors
  • Consists of three main subtypes with different actions:
Receptor
Location
Effect
Alpha-2A
Prefrontal cortex and locus coeruleus of the brain
  • Suppresses neuronal firing reducing the activity of ascending noradrenergic pathways:
    • Sedative and anxiolytic effects
  • Directly stimulate presynaptic α2A- and α2C-adrenoceptors in the spinal cord, thereby inhibiting the firing of nociceptive neurons
    • Analgesic (anti-nociceptive) effect
  • Reduces sympathetic outflow (sympatholytic action):
    • Reduces sympathetic tone (promotes hypotension)
    • Reduces cardiac sympathetic activity (reduces heart rate, cardiac output and myocardial oxygen consumption)
    • Reduces renal sympathetic activity (inhibits renin and vasopressin release, promotes diuresis)
Alpha-2B
Peripheral blood vessels
  • Vasoconstriction
Alpha-2C
Striatum and hippocampus of the brain
  • Unclear clinical effects
  • Postulated to have anxiolytic effects