Non - Catecholamines - Amphetamine

AMPHETAMINE
  • It is a synthetic sympathomimmetic drug with CNS stimulant and peripheral α and β adrenergic actions.
    • The mechanism of action is indirect, by releasing endogenous noradrenaline from adrenergic nerve terminals.
  • Due to amphetamine’s structural resemblance to nor adrenaline, it is transported into adrenergic nerve terminals by uptake1 process upon entry into the neuronal cytoplasm, it displaces noradrenaline from storage vesicles into the cytosol.
  • Some of the displaced noradrenaline is metabolized by MAO intraneuronally and the remaining is released into the synaptic cleft. This release process does not involve exocytosis and hence no need of action potential coupled Ca++ ion entry into the neuronal cytoplasm.
  • In addition to this amphetamine also blocks MAO and decreases uptake1 process, both of which increase the concentration of noradrenaline in synaptic cleft.
  • Pharmacological effects
    • As amphetamine acts by release of endogenous nor adrenaline, its pharmacological effects are similar to noradrenaline. In addition amphetamine has a powerful CNS stimulant effect.
    • The CNS effects include increased alertness, decreased fatigue, elevation of mood, ability to concentrate, euphoria, insomnia and anorexia.
    • Amphetamine stimulates the respiratory centre, especially if it is depressed. D-isomer of amphetamine (dextroamphetamine) is 3-4 times more potent than l-isomer in producing CNS effects.
    • However, l-isomer is more potent than d-isomer to produce peripheral effects. Noradrenaline in high doses or following prolonged use cause depression and fatigue.
  • Pharmacokinetics
    • Amphetamine is absorbed well following oral administration. Unlike catecholamines, it enters the CNS.
    • It has prolonged action as it is resistant MAO. It is mainly metabolized in the liver and excreted in urine.
  • Clinical uses
    • Has limited use in veterinary practice.
    • In humans used to treat depression, narcolepsy and hyperkinesis.
Last modified: Tuesday, 27 September 2011, 7:01 AM