Pharmacology/Introduction

So how does the brain work? What are Receptors and Neurotransmitters? What is an agnist and antagonist?

In this brief introductory section, we will be introducing these new terminologies.

The brain has billions of cells (i.e., neurones). Each neurone has thousands of connections (i.e., synapses). These neurones send electric signals to each other; they release chemicals (i.e., neurotransmitters) which carry the signals across the snaptic cleft.

• A neurotransmitter is a signaling molecule which crosses the synapse.
• A receptor is a protein that detects a specific checmical by binding to it.
• A hormone is a signaling moolecule, similar to the neurotransmittor (in fact, many chemicals are both; leaving the difference to tell between one and the other all the more blurry).
• A ligand is a molecule that binds to a receptor.
• We say a neuron is excitatory when it increases action potentials. So it sends signals (increases the signal).
• Likewise, we say that a neuron is inhibitory if it decreases the action potentials. So it blocks the signals (decreases the signal).
• An agonist is a ligand that stimulates a receptor. This mimics the neurotransmitter.
• And, lastly, an antagonist is a ligand that binds to a receptor without stimulating it. So this blocks the receptor.

From these definitions, we can conclude that antagonists block receptors and counteract agonists. So a receptor becomes excitatory if an agonist binds it; and becomes inhibitory if an antagonist binds it.

A nice example that gave is the following (taken exactly):

	Excitatory receptor	Inhibitory receptor
Agonist	(More signal) Nicotine	(Less signal) Alcohol
Antagonist	(Less signal) Diphenhydramine	(More signal) Caffeine

• Opioids (such as morphine, codeine, etc...) are full agonists at the $\mu$-opioid receptor.
• Alcohol is a GABA-agonist.
• Antihistimanies are histamine antagonists.
• Antipsychotics are dopamine antagonists at high doses, and serotonin antagonists at low doses.

Common Neurotransmitters

The most common excitatory neurotransmitter in the brain is glutamate (helps in learning and memory). "Glutamate is released by 80% of neurons.".

• PCP and Ketamine are glutamate antagonists. "They act at the NMDA glutamate receptor."
• Another NMDA antagonist is memantine (which is used for treating Alzheimer's disease).

What do glutamate agonists do? They tend to cause seizures since they excite the neurons.

The gamma-aminobutyric acid (GABA) neurotransmitter is the most common inhibitory neurotransmittor. Sleep and anxiety relief are the most common causes of the GABA agonists. Also, muscle relaxation and memory impairment.

The norepinephrine (NE) neurotransmitter causes excitement and the "fight/flight" response, along with fear.

The dopamine (DA) neurotransmitter increases happiness and alertness, and increases the rewards part of your brain, it is known as the salience neurotransmitter.

The serotonin (SER, 5-HT) neurotransmitter is known as the satiety neurotransmitter, it relieves depression and causes feelings of contentment.

The acetylcholine (ACh) neurotransmitter casues alertness, improves memory, and causes secretions of sweat and saliva.

The histamine neurotransmitter causes alertness, itchiness, rashes and stomach acid secretion.

Partial agonists is as the name suggests, an agonist but with partial effects. So partial agonists may be safer and have fewer side effects than full agonists. One example is buprenorphine (a $\mu$-opioid partial agonist); this is a lot safer than, say diamorphine (a full $\mu$-opioid agonist), but gives similar effects (i.e., pain relief).

References

MIT OCW, Drugs and The Brain, 2013