VPT 321: Veterinary Neuropharmacology (2+1)

DRUGS THAT AFFECT NORADRENALINE STORAGE

Reserpine

• It is a alkaloid obtained from the plant Rauwolfia serpentina. This blocks the transport of noradrenaline and other biogenic amines into synaptic vesicles, apparently by binding to the transport system. Thus the noradrenaline in the neuronal cytoplasm is metabolized by the enzyme MAO and is not stored in the synaptic vesicles.

Mechanism of action

• • Reserpine irreversibly binds to the storage vesicle in central and peripheral adrenergic neurons and blocks Mg⁺⁺-ATP dependant transport of biogenic amines-noradrenaline and dopamine from cytoplasm into the storage vesicles. Thus adrenergic nerve terminals cannot concentrate noradrenaline and its precussor dopamine in storage vesicles.
  • In addition it also causes leakage of stored noradrenaline into cytoplasm, where it is stored by MAO. Ultimately reserpine causes depletion of noradrenaline in sympathetic nerve endings.
• Pharmacological effects
  • Reserpine produces slowly developing fall in blood pressure, decrease in peripheral resistance and bradycardia. Renal and cerebral blood flow is unchanged due to suppressed sympathetic activity. High doses of reserpine causes depletion of catecholamines and 5HT in brain an produces sedation an depression.
• Side/adverse effects
  • Because of suppressed overall sympathetic activity, there is predominance of parasympathetic over activity in many systems. This causes bradycardia, diarrhea, increased gastric acid secretion an miosis.
• Clinical uses: Rarely used because of adverse effects.