Unit 1: Neuropharmacology

Question 1

What are drugs?

Answer 1

Drugs =
- a chemical substance—either naturally occurring (eg. nicotine from tobacco) or synthesized in a lab (eg. fentanyl)
- when consumed, will change an organism’s physiology and/or psychology
- have a defined chemical structure
- a 3D object with (+) and (-) charge—it will fit into cell receptors with the same 3D size, shape and electrical charge(s)
- developed based on pre-existing, naturally-occurring receptors

Question 2

How do drugs work?

Answer 2

All drugs have a target—they bind to receptors (proteins) and change their shape and activity

Change in receptor activity = change in neuron activity = change in brain function

Question 3

Orphan Receptors

Answer 3

Cell receptors whose purpose = unknown

Question 4

What does ADME stand for?

Answer 4

Administration: the method of administration will affect the rapidness of a drug’s onset
- intraveinously/inhalation: rapid onset
- intramuscular/ingestion: slower onset

Distribution: once a drug reaches the bloodstream, it is distributed fairly evenly throughout the body

Metabolism: enzymes exist to break down nutrients and to eliminate toxins—some drugs (pro-drugs) depend on the body’s metabolism to work
- (eg. codeine = a pro-drug wherein the body converts it to active morphine)

Elimination: a drug will stop working once it is eliminated from the body

Question 5

Cell Receptors

Answer 5

A receptor is a protein

Receptors are located at the surface of the cell—they signal to the cell by changing shape when they bind their ligand or drug

When the neurotransmitter/drug binds to the channel, it opens a pore allowing ions to flow in or out of the cell

Lock and Key analogy
Lock = a receptor
Key = a drug
If the key (drug) is the right size and shape, it can turn the lock (receptor) and influence the activity of that receptor.

Question 6

How long do drugs act?

Answer 6

How long do drugs act?
- depends on the drug and dosage
- drug binding is usually transient (reversible)
- once unbound, a drug can bind to another receptor or be eliminated from the body
- some drugs bind irreversibly—only way to stop their action is to make a new receptor (hours)

Drug Presence
- if a drug is continuously present, the cell will adapt
- receptor upregulation: more protein made (when the drug is an antagonist)
- receptor downregulation: less protein made (when the drugs is an agonist)

Question 7

What is an agonist?

Answer 7

An agonist is a medication that mimics the action of a signal ligand by binding to and activating a target receptor

Question 8

What is an antagonist?

Answer 8

An antagonist is a medication that binds to a target receptor without activating it, and instead inhibits the receptor’s ability to be activated by another ligand

Question 9

Agonist/Antagonist
≠
Excitatory/Inhibitory

Answer 9

The agonist/antagonist labels ARE NOT necessarily indicative of the polarization action of a neuron.

The inhibitory/excitatory characteristic is determined by what ions are influencing electrical charge.

Positive ions (Na+, Ca+, K+) = excitatory effect
Negative ions (Cl-) = inhibitory effect

eg.
- agonist = activator of a receptor
- alcohol = agonist of GABA receptors (inhibitory neurotransmitter) – alcohol stimulates GABA, which

Question 10

Analogy for Neurons: The Battery
(pt 1)

Answer 10

Neurons are like rechargeable batteries that are continually storing and releasing energy:

Batteries have two chambers that separate chemicals with opposite charge
- negative charge (-) = molecules with extra electons
- positive charge (+) = molecules lacking electrons

Electrons are drawn to the positive chamber by electrostatic attraction—energy is only released when a conductive wire connects both chambers, allowing (-) electrons to flow to the (+) chamber. When all neg charged chemicals are gone, the battery is dead.

Question 11

Analogy for Neurons: Neuron Battery
(pt 2)

Answer 11

Neurons are like batteries that store energy by continuously pumping charged ions like (Na+), (Ca+) and (Cl-) out of the cell—meaning there are more (+) ions outside than inside

Positive and negative ions are drawn to each other by electrostatic attraction, but are prevented from interacting by the cell membrane—when the membrane opens, (+) ions rush into the cell, equalizing the electrical gradient, creating an electrical current. Like a battery, the neuron loses its stored energy

Question 12

Analogy for Neurons: Recharging the Neuron Battery
(pt 3)

Answer 12

The neuron battery must be recharged by pumping charged ions back across the membrane—using energy in the form of ATP, generated by mitochondria in the neuron

ATP = adenosine triphosphate

This is why the brain consumes more energy than any other organ—it is constantly recharging the billions of batteries in our brain

Question 13

Positive Ions

Answer 13

Sodium (Na+), Calcium (Ca+), Potassium (K+)

Question 14

Negative Ions

Answer 14

Chloride (Cl-)

Question 15

Resting Membrane Potential
(Polarized Neuron)

Answer 15

A neuron that is in the charged state and ready to fire

Polarized neuron: (+) and (-) ions are kept separate

Question 16

Depolarization

Answer 16

A rapid rise in potential. A neuron is depolarized when an excitatory neurotransmitter opens the voltage-gated sodium channel, allowing (Na+) ions to flood into the neuron.

If enough depolarization happens, the neuron will fire, sending an action potential (electrical current) down the axon.

A neuron will remain polarized if enough inhibitory neurons reach the dendrites at the same time—hyperpolarization counteracts depolarization.

Question 17

Action Potential

Answer 17

An action potential is a rapid change in voltage across a membrane caused by the depolarization of a neuron.

This electrical current begins at the axon hillock, travels down the myelinated axon, and ends at the axon terminal. When the potential reaches the terminal, this triggers calcium (Ca+) channels to open—(Ca+) causes synaptic vessicles to release their neurotransmitter.

Question 18

Repolarization

Answer 18

Once a neuron is depolarized and has fired, it can’t fire again until it is recharged. Repolarization is the process of re-establishing a membrane potential by using ATP to push ions out of the cell.

Question 19

Hyperpolarization

Answer 19

A hyperpolarized neuron is one that is less likely to fire. A neuron becomes hyperpolarized when inhibitory neurotransmitters offsets the amount of positive ions in the membrane.

Question 20

Presynaptic Neuron

Answer 20

A presynaptic neuron is the cell that sends information (releases neurotransmitters upon depolarization)

Question 21

Postsynaptic Neuron

Answer 21

A postsynaptic neuron is the cell that receives information (collects neurotransmitters as a result of depolarization).

Neurotransmitters bind to receptors on the postsynaptic neuron. If the transmitter is:

Excitatory : the postsynaptic neuron will generate a new action potential.
- eg: glutemate, acetylcholine

Inhibitory : the postsynaptic neuron is quieted and becomes less likely to generate an action potential
- eg. GABA, glycine

Question 22

Pharmacology

Answer 22

Pharmacology: the study of drugs and their actions on the body

Question 23

Target

Answer 23

The specific protein that a drug physically interacts with and changes its function

Question 24

Mechanism of Action

Answer 24

The specific biochemical interaction through which a drug substance produces its pharmacological effect

A current understanding of a drug’s target, and how the interaction between a drug and receptor facilitates a change in neuron activity/brain function

Question 25

Drug Potency

Answer 25

Concentration or amount of drug required to produce a defined effect

Drugs with higher potency:
- have better affinity for their receptors
- are usually selective for one type of receptor

Question 26

Drug Affinity

Answer 26

The extent or fraction to which a drug binds to receptors // the strength of attraction between a drug and receptor
- “goodness of fit”
- how much energy is needed to pull the drug away from the receptor

High Affinity drugs:
- have a shape that hugs the contours of the protein and makes numerous electrostatic contacts to hold in place
- less drug required to achieve defined effect
- high effectiveness and longer duration
- are usually very selective, interacting with one specific target

Low Affinity drugs:
- more drug required to achieve defined effect
- have low effictiveness and short duration
- usually non-selective about their target

Question 27

Drug Selectivity

Answer 27

Refers to how many proteins (target receptors) are affected by the drug

Highly Selective “clean” drug: only binds to one or a few proteins—has a high affinity for its target

Non-Selective “dirty” drug: has many targets that it interacts with; similar affinity for any target