Questions about Serotonin Antagonist and Reuptake Inhibitors and how they produce their therapeutic effects

[matthurry]

Hi guys, I'm doing a biology access course (this current module is about neurotransmitters and drugs), and i'm a little stumped by this one. All of the info i've read online is too complex for my current level of understanding, but here is what I (kind of) understand so far. Also, i'm not that bothered about getting the answer 'correct', but about understanding this stuff, as it seems a little contradictory to me.

• So, Antagonist drugs work by binding to the receptor of a neuron WITHOUT activating it, thus increasing the concentration of the neurotransmitter in the synapse as NTs cannot bind to these receptors - what I don't understand about this, and I guess it's a larger question about how NTs work, is how simply increasing the concentration of a certain NT in the 'synapse' (which I take to be the space between one neuron and the next) actually creates an effect on the human being. Isn't it the action of the NTs binding to receptors which causes effects, such as a change in mood or the ability to think clearly (cognition)? Why does blocking receptors artificially have any effect?
• Re-uptake inhibitors work by preventing re-uptake pumps on the neurons AXON TERMINAL from absorbing unused NTs back into the neuron which released them - thus more NTs will remain in the synapse for longer - and presumably eventually more will bind to the receptors on the dendrites on the next neuron because there are more molecules available?

What I really don't get is how these two actions is having any therapeutic affect on a patient. Both seem to increase the availability of NTs in the 'synapse', but one of them prevents the NTs from binding to target receptors! Which I'm finding pretty hard to understand. Is it simply having a NT, ie serotonin, in the synapse, the 'thing' that causes therapeutic affects?

 

As way of example - SARIs (serotonin antagonist and re-uptake inhibitors - Trazadon is one example i've read about) are described, which apparently treat depression. Maybe i'm going too far in my research - but apparently these 'work' by antagonising certain (ie 5HT-2A) receptors, agonising others (ie 5HT-1A), and blocking serotonin re-uptake. Why would you want block the activity of some receptors, stimulate activity in other receptors, and also increase the availability of serotonin overall in the synapse? And how are these actions resulting in an increased feeling of well being?

 

Sorry if it's a long question - and i'm not expecting answers, but guidance. This stuff is interesting but seems counter-intuitive. I'm also not really sure on the basics of why a NT like Serotonin would actually make a human being feel good by a biologic reaction in the brain! Thanks so much for reading, and any help / understanding would be so appreciated 😄