> wishing you good health scott.
Thanks John.
I apologize for the mistake I made in my explanation.
It is extremely important to understand the concept of feedback loops and homeostasis.
The method by which most neurons manage how much neurotransmitter to synthesize and release is to monitor how much is floating around outside the cell. In the case of the synapse, the sensors that do the monitoring are called autoreceptors, and are located presynaptically on the first (sending) neuron. When most of these receptors are occupied by the neurotransmitter molecule as concentrations grow, it tells the presynaptic cell to stop making so much of it and to reduce its release. Thus the concentration of neurotransmitter in the synapse begins to decrease. When it gets too low, most of the autoreceptors are empty. The drop in autoreceptor occupancy signals the neuron to then increase the synthesis and release of neurotransmitter. This is an example of a negative feedback loop. It facilitates the maintenance of consistency in synaptic neurotransmission. This is an example of homeostasis.
Remeron (mirtazapine) acts to block the presynaptic autoreceptors from detecting norepinephrine (NE) in the synapse. It occupies the autoreceptor, but does not stimulate it. This is called receptor antagonism, with Remeron being the antagonist. As far as the presynaptic neuron is concerned, the concentration of NE is too low, so it keeps synthesizing and releasing NE, even while synaptic concentrations continue to rise. The homeostasis is disrupted.
The NE autoreceptor that Remeron blocks is of the subtype NE alpha-2. It is therefore an antagonist of that receptor. Remeron is selective because it does not bind to other subtypes of NE receptors. Postsynaptic NE receptors located on the second (receiving) neuron remain available to be stimulated by the increasing synaptic concentrations of neurotransmitter. Overall NE activity increases, at least for awhile. However, in order for this to happen, dosages of Remeron must be high enough. This probably accounts for why higher dosages of Remeron (45 - 90 mg/day) become less sedating and more antidepressant.
- Scott
![[collapse]](http://www.dr-bob.org/images/babble/hide.gif)
this signature | Show by default | Change to hide (next time)Some see things as they are and ask why.
I dream of things that never were and ask why not.
- George Bernard Shaw