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Altering neurotransmission 2a: pre-release

Altering neurotransmission 2a: pre-release
6.4
So we’ve met this structure before. This is the synapse, and we previously looked at how this cell, presynaptic cell, could communicate with this, the postsynaptic cell, by this process of releasing chemical neurotransmitter substances. Now, although this is a highly-simplified version of what we actually know to be the processes that go on in synapses, we can still see that there are plenty of processes here where we could interrupt or change the function. And these processes are actually where many of the drugs that have an action on the nervous system work. And these drugs can be for good, for therapeutic purposes, or they can cause problems.
51.5
So what I want to do is to just look at some examples using drugs that you may well have heard of to illustrate how some of these processes can be affected by drugs. The first thing that we have to think about is that here in the presynaptic terminal, we have these vesicles full of neurotransmitter molecules, which are represented here by the dots. This is obviously not to scale. And these neurotransmitter molecules have to come from somewhere. They have be synthesised, produced within the cell. And one of the ways in which drugs can act is to affect this synthesis process.
90.7
To give you an example, for Parkinson’s disease, patients are given a drug called L-dopa And L-dopa is a precursor for dopamine. And dopamine is the neurotransmitter that’s particularly linked to Parkinson’s disease. So we can affect the level of synthesis here because we can provide terminals with more of that precursor. So we can affect the level of neurotransmitter that is present in the presynaptic terminal. Now, the other thing that is obvious from this diagram is that our ability to put these molecules into these vesicles and therefore store them so they can be released when it’s appropriate, is absolutely critical to the process. So can we think of any examples of drugs which interfere with this process?
144.2
Well, one of the drugs that does is something you may have heard of, amphetamine. Now, amphetamines we consider not to be therapeutic, but to be drugs that may be abused. So what happens to amphetamine? How does it affect this process? The answer is amphetamine gets into the terminals and it gets into the vesicles. And in so doing, it displaces the neurotransmitter out into the cytoplasm of the terminal. Now, once it’s out here, that dopamine or noradrenaline, various transmitters, can then find their way out of the terminal and of course, have their action. So this displacement activity of amphetamine is what is responsible for the effects that we see.
201.9
Now, what we know in the normal process of neurotransmission is that these vesicles containing the neurotransmitter need to fuse, as I’ve represented here, with the membrane in order to allow normal release of the neurotransmitter. Now, as you might imagine, the process of a vesicle fusing with this, the cell membrane, is actually rather complex. But we know that there are some drugs which can interfere with that process. And of course, clearly, therefore, what they’ll do is interfere with our ability to reduce neurotransmitter. Now, there are many examples of drugs that do this. Many would be considered neurotoxins, toxins affecting the normal activity of the nervous system. Perhaps a surprising one for us to think about is Botox, OnabotulinumtoxinA.
257.8
So the people Botox people are having injected into their faces to reduce wrinkles acts by preventing the binding of vesicles and the merging of the vesicle with the cell membrane and therefore preventing the release of the neurotransmitter.

An explanation of how chemical neurotransmitters can affect cell function at the synapse, focusing on processes in the pre-synaptic terminal.

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