MOA of tyramine?

Discussion in 'Step I' started by studylol, 09.30.14.

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  1. studylol

    studylol 2+ Year Member

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    Tyramine is an indirect sympathomimetic. "These indirect agents may have either of two different mechanisms: (1) they may displace stored catecholamines from the adrenergic nerve ending (eg, the mechanism of action of tyramine)..."

    I don't understand. It's not as simple as cramming stuff onto a shelf, and having the ends fall off. How is displacement of catecholamines done? And why does it cause NE release?

    Thanks!
     
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  3. Transposony

    Transposony Do or do not, There is no try 5+ Year Member

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    1. Tyramine is derived from Tyrosine fermentation.
    2. Tyramine is normally metabolized in the gut and Liver by MAO (First pass metabolism)
    3. In patients on MAOI, tyramine is not metabolized and it competes with tyrosine for transport into the nerve terminal.
    4. Inside the the nerve terminal, it is transported via VMAT (vesicular monoamine transporter) into synaptic vesicles, thereby displacing norepinephrine.

    Hope this helps.
     
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  4. seminoma

    seminoma 2+ Year Member

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    And it causes NE release by reversing the concentration gradient.

    No MAO (because patient taking MAOI) in the presynaptic cell --> intracellular NE > synaptic cleft NE --> diffusion of NE out of presynaptic cell.
     
  5. NeuroLAX

    NeuroLAX Discere faciendo 2+ Year Member

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    Where did you find this info?
     
  6. seminoma

    seminoma 2+ Year Member

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    Nowhere. Just normal physiology principles. If NE can't be metabolized and can't be stored it will exit the cell.
     
  7. DeeJay2728

    DeeJay2728 5+ Year Member

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    Anything that increases the Mobile Pool of NE (the NE inside presynaptic cell, but NOT the NE in the vesicles) will cause either Increased Diffusion of NE out of Presynaptic cell or cause Reversed usage of the Reuptake pump.
    One of the major functions of MAO is to regulate the NE Mobile Pool (it prevents an increased amount of NE inside cell). If this gradient isn't maintained NE will diffuse out or use the reuptake pump.

    MAO degrades both NE and Tyramine (therefore increasing mobile pool of NE when eating cheese)
    MOAI's (increase Mobile pool of NE)
    Now imagine a pt eating cheese AND taking MAOI's (Massive increase of NE mobile Pool ---> Massive release of NE)
     
  8. studylol

    studylol 2+ Year Member

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    Appreciate the responses. I'm curious how NE can simply diffuse out of the cell. Why is there a receptor for this?
     
  9. DeeJay2728

    DeeJay2728 5+ Year Member

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  10. studylol

    studylol 2+ Year Member

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    Thanks, but is my receptor question addressed there? I might be missing it.
     
  11. DeeJay2728

    DeeJay2728 5+ Year Member

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    There's no receptor. The increased gradient causes it to diffuse out.
     
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  12. Transposony

    Transposony Do or do not, There is no try 5+ Year Member

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    Yes, NE simply diffuses out of the presynaptic nerve terminal.
    Tyramine stimulates norepinephrine release from sympathetic nerve terminals by reverse transport through NET. It also prevents re-uptake of NE through NET.
    This released NE leaks out from the cytoplasm and is responsible for the sympathomimetic effect of tyramine.
    Remember, there is no MAO in the mitochondria to metabolize the tyramin induced and/or normal NE leak from vesicles into the cytosol.
    There is no other receptor involved except on the postsynaptic membrane as usual for NE.
     
    Last edited: 10.02.14
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