Lesson 7: Drugs

Question 1

Which two neurotransmitters do 99% of nerons release?

Answer 1

Glutamate and GABA

Question 2

What are the characteristics of glutamate?

Answer 2

It encourages spiking (excitatory sodium ions) and membrane depolarization
- agonists: seizures and excitotoxicity
- antagonists: dissociative anaethetics

Question 3

What are the characteristics of GABA?

Answer 3

It encourages less spiking (inhibitory: chloride ions) to occur, and membrane hyperpolarization
- antagonists: seizures
- agonists: anaethetics, anticonvulsants, muscle relaxants, sleeping pills, etc.

Question 4

What are the four classic neurotransmitters (that we call neuromodulators)?

Answer 4

Acetylcholine, dopamine, serotonin, and norepinephrine

Question 5

Why do we call acetylcholine, dopamine, serotonin, and norepinephrine neuromodulators?

Answer 5

Because they are not released from every neuron in the brain
- they act on metabotropic receptors (NOT ionotropic receptors)
- they don’t produce simple excitatory or inhibitory effects in the CNS
- they can diffuse short distances outside of the synapse and influence the activity of neighboring neurons

Question 6

What is the synonym of norepinephrine?

Answer 6

Noradrenaline

Question 7

What is the synonym of epinephine?

Answer 7

Adrenaline

Question 8

What are the conventional neurotransmitters and their characteristics?

Answer 8

Glutamate, GABA, dopamine, serotonin, acetylcholine, and norepinephrine
- made locally in axon terminals
- packaged in small synaptic vesicles
- only these can activate ionotropic receptors (and metabotropic receptors)
- recycled and reused
- heavily regulated

Question 9

What are neuropeptides and their characteristics?

Answer 9

They are strings of amino acids (10-30x bigger than the classical neurotransmitters)
- NOT made locally: made in the cell body
- packaged in large dense core vesicle
- ONLY activate metabotropic receptors (NOT ionotropic receptors)
- NO RECYCLING of neuropeptides
- may diffuse long distances

Question 10

What are lipid-based signaling molecules?

Answer 10

They are synthesized and released on demand: post-synaptic neuron makes the decision (sends feedback) to the pre-synaptic neuron
- only activate metabotropic receptors

Question 11

What are the monoamine neuromodulators?

Answer 11

Serotonin, dopamine, norepinephrine, and epinephrine

Question 12

What is the name of the only protein that packages the monoamine neuromodulators into synaptic vesicles?

Answer 12

The vesicular monoamine transporter (VMAT)

Question 13

Which monoamines are catecholamines? Which are indolamines?

Answer 13

Catecholamines: dopamine, norepinephrine, epinephrine
Indolamines: serotonin

Question 14

What does acetylcholine cause when introduced in excessive amounts in our system?

Answer 14

Acetylcholine causes muscle contractions (such as paralysis)

Question 15

What neurotransmitter do motor neurons generally release?

Answer 15

Acetylcholine

Question 16

What neurotransmitter do sensory neurons generally release?

Answer 16

Glutamate

Question 17

How does venom enter our cells?

Answer 17

Venom sneaks in by attaching to the membrane and then goes into the cell
- Black Widow Spider venom will act like a calcium ion - doesn’t need any action potential to open the vesicle, so acetylcholine will continuously be released

Question 18

What is neostigmine?

Answer 18

A drug that inhibits the activity of acetylcholinesterase, which is the enzyme that breaks down acetylcholine in the synaptic cleft
- it causes acetylcholine to stay around longer in synapses, causing more muscle contraction

Question 19

What is an agonist receptor?

Answer 19

A drug that directly or indirectly increases the activity of postsynaptic receptor proteins

Question 20

What is an antagonist receptor?

Answer 20

A drug that directly or indirectly decreases the activity of postsynaptic receptor proteins

Question 21

How do direct agonists/antagonists affect postsynaptic receptor activity?

Answer 21

They directly bind to postsynaptic receptors

Question 22

How do indirect agonist/antagonist affect postsynaptic receptor activity?

Answer 22

The proteins they bind to are not postsynaptic receptors
- they bind to other proteins

Question 23

What are antipsychotics?

Answer 23

A class of drugs used to treat psychosis
- they bind to more than one type of receptor, but one action they all have in common is they directly block the dopamine D2 receptor, which is an inhibitory metabotropic receptor expressed by neurons all over the brain

Question 24

WHat is the difference between the drugs that cause hallucinations and those that do not?

Answer 24

Those that do: activation of the g protein ‘Gi/o’ which results in hallucinations

Question 25

What is biased agonism?

Answer 25

When a metabotropic receptor ligand causes the receptor to preferentially activate one type of intracellular g protein, whereas another ligand at the same receptor might preferentially activate a different g protein

Question 26

What is a competitive agonist?

Answer 26

It activates the receptor by binding where the neurotransmitter normally binds
- partial competitive agonist: less postsynaptic receptor activity than we normally would (similar to full antagonist)

Question 27

What is a competitive antagonist?

Answer 27

It attaches to the same binding where the neurotransmitter normally binds, but it doesn’t activate the receptor
- competitive antagonists are full antagonists

Question 28

What is affinity when talking about a binding site?

Answer 28

Affinity refers to the probability and tightness of ligand-receptor binding

Question 29

What is a non-competitive agonist?

Answer 29

Fully or partially activates the receptor

Question 30

What is non-competitive binding?

Answer 30

When a drug binds to a receptor at a site that does not interfere with the binding site of the principal ligand
- it is possible for a neurotransmitter to bind on one site of a receptor while a drug binds on another

Question 31

What is a non-competitive antagonist?

Answer 31

It fully blocks receptor activation.
- it doesn’t compete for the neurotransmitter binding site

Question 32

What are allosteric modulators?

Answer 32

Non-competitive drugs that only influence receptor activity when the neurotransmitter is also bound to the receptor
- negative: less neurotransmitters can come in (inhibitory)
- positive: amplify neurotransmitters that come in (excitatory)

Question 33

How are classical neurotransmitters made?

Answer 33

They are mad ein axon terminals from precursor molecules (generally amino acids)
- the synthesis of neurotransmitter from precursor molecules is controlled by enzymes
- once made, neurotransmitters are packaged into synaptic vesicles

Question 34

What controls the clearance of neurotransmitters from the synapse?

Answer 34

By reuptake transporter proteins and enzymatic deactivation

Question 35

What are drugs that block the reuptake of catecholamine neurotransmitters and transporters?

Answer 35

Methylphenidate, cocaine, adderall, and crystal meth