Hello hello Subi has an exam today so she's gonna rant to you about neuro drugs!!!!!!! So neuro drugs are exogenous substances that, when administered will act on the nervous system to change it's function in some way!!!These drugs can act specifically on a certain

Neurotransmitter system like serotonin or acetylcholine or have a more general effect ! For the ease of explaining I'm just gonna go through the different neurotransmitter we've focused one !!!!

Okay so Serotonin!!!! We all know it, idk about u but for me the S in BTS also stands for serotonin considering the "serotonin boost" I get when I see them . Serotonin is a neurotransmitter that is derived from tryptophan! Tryptophan undergoes a series of chemical changes

Leading to serotonin or 5HT! The transmitter is implicated in a lot of things, including hallucinations, sleep, mood and emotion, behaviour, memory, autonomic control and migraines

For example, did u know LSD is actually an analogue for 5HT which means it can bind to serotonin receptors to activate them!!! It can cause auditory and visual hallucinations

As for sleep, there's an area in the brain stem called the raphe nucleus where u have lots of 5HT. And a lesion of that area has actually shown decreased sleep!!!

Serotonin receptors are also found in a lot of the areas in the brain responsible for memory such as the hippocampus and the cortex and in fact the decrease in 5HT for Alzheimer's patients have been linked to cognitive impairment

Additionally, genetic differences in serotonin receptors have shown differences in memory task performance

Now serotonin has a range of receptors and each receptor kinda has a different role and function in the brain and can be implicated in different disease states.

Okay now we gonna move onto noradrenaline (NA) . Noradrenaline is synthesised from the chemical tyrosine. Tyrosine actually first synthesises dopamine which in turn is synthesised into noradrenaline!!! Cool right???

Noradrenaline has a widespread effect in the brain but has very localised nuclei. It's implicated in sleep, attention, arousal - so like fear and stress, learning and memory, mood and blood pressure regulation

So when u think stress and fear, NA is in fact elevated during the stress response. And for memory, the more noradrenaline u have, the better your memory is gonna be

When readings of neurons from the locus coereleus (which is the main nucleus for this transmitter) is taken, u see an increase in NA after arousal and a decrease during sleep

Okay moving on to acetylcholine!! Synthesised from choline and acetyl coenzyme A, acetylcholine has an enormous effect on the body especially through the autonomic system. It has various implications in the CNA as well including in memory, attention, movement, addiction and mood!

Acetylcholine (ACh) has been shown to be associated with the loss of memory in Alzheimer's patients wherein there is a degeneration of the cholinergic neurons (neurons that work w/ ACh). Not only that, drugs blocking ACh action has shown to induce memory deficit!!

ACh has two types of receptors, muscarinic and nicotinic! And yes the latter is implicated in nicotine use and abuse

Nicotine infact has a very profound effect on the CNS. It's involved in pleasure, reward and addiction and regular exposure to it can induce changes in receptor numbers which can thus affect the sensitivity to the drug

ACh is also implicated in a lot of disease states such as glaucoma, OBD, Myesthenia Gravis and can be a target for a lot of drugs which can result in a lot of unpleasant side effects

Okay let's go to dopamine now!!! We all know dopamine! It's a derivative of tyrosine and is implicated in different pathways which can have very different functions.

You've got the Mesolimbic/Mesocortical pathway, the Nigrostriatal pathway, and the tuberoinfundibular pathway (just to name a few)

Dopamine can affect Movement, Memory, Mood, Reward, Addiction and maybe even vomiting (??????)

Now Dopamine and movement is a very important correlation esp considering disorders such as Parkinson's. It is infact the degeneration of these dopaminergic neurons that are responsible for the motor deficiencies. This is in the Nigrostriatal pathway

Amphetamine which also affects dopamine also induces stereotypical and repetitive behaviours. This is in the Mesolimbic pathway!

Dopamine can be used to treat a lot of disorders because of how widespread it's effect can be but since it's very much implicated in the reward pathway, you also have to be wary of addiction.

Hehehe okay before we move onto some very different neurotransmitters, let's look into the different things we can target when we look at drugs for the transmitters I've just talked about

So a lot of the things do crossover for these systems, that's why I'm explaining them all together. Drugs used to target these systems can affect a range of things that affect the transmitters' release into the system.

This includes synthesis, transport, reuptake, metabolism and receptors!!

So for synthesis, the transmitter may have a rate limiting enzyme that can be targeted to affect the production of the transmitter. Serotonin, for example, has tryptophan hydroxylase which can be inhibited by PCPA, reducing serotonin in the pre synaptic neuron!

Noradrenaline - tyrosine hydroxylase - AMPT inhibits the enzyme to reduce synthesis
Dopamine - tyrosine hydroxylase

Transport! So this is actually the intake of the transmitters into vesicles which are responsible for transporting the transmitters to the end of the axon for release into the synapse.

Serotonin, Noradrenaline and dopamine all have the same transporter VMAT which is inhibited by Reserpine! The ACh transporter can also be inhibited by vesamicol

Okay Reuptake is an important one. Neurons have transporters on their membrane responsible or taking back up any transmitters in the synapse. This reuptake process can be blocked or enhanced by drugs to affect the amount of transmitter in the synaptic cleft

Serotonin - SERT (the transporter) - SSRIs SNRIs can inhibit which increased levels of serotonin in the synapse, can be used to treat depression and anxiety! - MDMA or Ecstasy can also work on these transporters to elevate serotonin causing mood elevation and altered perception

NA - NET - similar to SERT, antidepressants mainly inhibit function of the transporter. Cocaine and amphetamine also work on these transporters to enhance transmitter levels in the synapse.

ACh - choline transporter - this one works a bit differently because ACh is broken down in the synapse and it's the metabolite, choline, that is taken up by the transporter, drugs such as hemicholinium can inhibit reuptake of choline which actually decreases the production of ACh

DA - DAT - similar to SERT and NET -amphetamine and cocaine also affect the function of the transporter to increase dopamine

Okay now metabolism!! Transmitters can also be broken down by enzymes in the synapse to stop the function of transmitters. These enzymes can be targeted by drugs as well to treat disorders!

5HT - Monoamine oxidase (MAO) is the main enzyme that metabolises serotonin - the action of this enzyme can be inhibited by drugs and these drugs are used as antidepressants.

NA - COMT and MAO are responsible for the metabolism of NA and can both be targeted by drugs, tropolone is a COMT inhibitor.

Acetylcholinesterase - hydrolyses ACh - drugs that inhibit the transporters have been used to treat various disease states such as myasthenia gravis