Alpha-2 agonists vs antagonist mechanism?

[Daitong]

Hi,
Apparantly, "the mechanism of action of α2 blockers is an increased release of norepinephrine and serotonin from presynaptic vesicles. Remember that activating α2 receptors inhibits the release of these."

I don't get this. I thought the alpha-2, just like any adrenergic receptor, would require the release of NE/E to become activated, so wouldn't the mechanism of alpha-2 blockers INCREASE activity?

I feel like I'm missing a fundamental piece of the puzzle; could some one please explain it?

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[illinichief89]

Alpha-2 receptors are found, among other places, on the terminals of postganglionic sympathetic neurons. When stimulated, they act as negative feedback on the neuron to tell it to stop releasing NE/5-HT. That's why a drug like clonidine, an alpha-2 agonist, is linked to depressive symptoms when administered because there is less release of NE/5-HT in the brain, which is hypothesized to be the problem in depression. If you gave an alpha-2 blocker, that would inhibit the inhibition of NE/5-HT release provided by the alpha-2 receptors;thus, it would actually increase the release of NE/5-HT.

 

[wjs010]

I thought alpha 2 was found (sometimes) on post gang, but mainly pre gang. Hence, when you give an alpha 2 agonist, it is likely you CAN get a transient hypertension, but then you get lowered BP because alpha 2 MAINLY inhibits presynaptic secretion