Lecture 1- Introduction

Question 1

What are the 5 types of neurotransmitters? (briefly)

Answer 1

1. Amino acids
2. Catecholamines
3. Peptides
4. Lipids/steroids
5. Small molecules

Question 2

Give examples of the 5 types of neurotransmitters?

Answer 2

1. Amino acids- Glutamate, GABA
2. Catecholamines- Noradrenaline, Dopamine, ACh
3. Peptides- Substance P, neuropeptide Y
4. Lipids/steroids- Endocannabinoids, androgen/oestrogen
5. Small molecules- Nitric oxide (NO)

Question 3

For amino acids, give:

1. Example?
2. Target?
3. Main Role?

Answer 3

1. Glutamate, GABA
2. Ligand-gated ion channels, G-protein coupled receptors
3. Fast/slow excitation and inhibition

Question 4

For Catecholamines, give:

1. Example?
2. Target?
3. Main Role?

Answer 4

1. Noradrenaline, Dopamine, ACh
2. G-protein coupled receptors
3. Fast/slow transmission & modulation

Question 5

For peptides, give:

1. Example?
2. Target?
3. Main Role?

Answer 5

1. Substance P, neuropeptide Y
2. G-protein coupled receptors
3. Modulation

Question 6

For lipids/steroids, give:

1. Example?
2. Target?
3. Main Role?

Answer 6

1. Endocannabinoids, androgen/oestrogen
2. G-protein coupled receptors, Nuclear and membrane receptors
3. Modulation & plasticity

Question 7

For small molecules, give:

1. Example?
2. Target?
3. Main Role?

Answer 7

1. Nitric oxide (NO)
2. Multiple? Action at a distance?
3. Modulation

Question 8

Define excitation?

Answer 8

fast (relatively) post-synaptic excitatory potential (EPSP)

Question 9

Define inhibition?

Answer 9

fast (relatively) post-synaptic potential (IPSP)

Question 10

Define modulator?

Answer 10

not clearly defined – used to be an effect which did not give rise to excitation or inhibition, but “affected their effectiveness” - amplification or reduction of other activity – but now includes up/down regulation of transmitter release, action outside synapses (NO and GABA?) – merges into longer term neurotrophic effects

Question 11

Define agonist?

Answer 11

• occupy and activate the receptor
• Full agonist – sub 100% occupancy elicits full effect
• Partial Agonist – 100% occupancy fails to produce full effect

Question 12

Define antagonist?

Answer 12

• lit. “prevents agonist activity”
• Competitive antagonist “competes” with agonist for receptor
• Irreversible antagonist – blocks the receptor but dissociates slowly or not at all – cannot be “competed with”
• Alone has no effect

Question 13

Define allosteric effects

Answer 13

•drugs may bind to sites not directly involved in the agonist/receptor area, but modulate (up or down) either the affinity or efficacy of the agonist

Question 14

Define Constitutive receptor activation

Answer 14

•Some receptors are in an active state, even in the absence of a ligand – proportion is very variable, dependent upon receptor type, location and (patho)physiology.

(has a tone even in absence of ligand)

Question 15

Define inverse agonist?

Answer 15

drug which bind to the (constitutive active) receptor and reduce the “effect” (unlike true antagonist)

(NOT THE SAME AS ANTAGONIST)

Question 16

Define spare receptors?

Answer 16

•possible that more receptors are available than would be required to elicit a full response from agonist

Question 17

What are the time domains of the neurotransmitters?

Answer 17

Question 18

How is the CNS protected?

Answer 18

Brain and spinal cord are protected in a “fluid-filled” bag – physical protection against movement/trauma – but also chemical isolation – bathed in cerebrospinal fluid (CSF)

Question 19

What is the blood-brain barrier?

Answer 19

It’s a physical barrier where the blood is “sealed-off” from interstitial fluid = CSF. There are tight junctions and structured to seal it off.

The barrier needs energy: Active transport for things like glucose etc

(Entrance to drugs restricted, depends on lipophilic nature, or “fit” to existing pumps)

Question 20

When does the blood-brain barrier appear to leak?

Answer 20

In experimental animals, after an IV injection of an antibiotic (thienamycin, not in current use), plasma levels begin to drop immediately (expected) – the very small amount that “partitions” into the CSF occurs a little later (~1/2 hour) – however, during inflammatory conditions, such as meningitis, the barrier becomes leaky, and the drug crosses easily, with its CSF levels paralleling the plasma levels.

Question 21

What is CSF?

Answer 21

CSF is a plasma transudate, continually produced by the choroid plexus of the ventricles and returned to the circulation through the arachnoid villae – acts a cushion but also reservoir for metabolites etc.

Question 22

Why does the brain get so much of the body’s glucose?

Answer 22

Blood supply provides oxygen and glucose (actively). The brain uses glucose as its only energy source. Can’t use anything else if glucose runs out so the body delivers loads to the brain to make sure.

Question 23

How are drugs for the brain different and more difficult?

Answer 23

Because of how complicated circuits are, the pharmalogical profile worked out by animal testing does not always fit the therapeutic effect.

Many drugs at the moment are quite non-specific, effecting many targets. Can be dose-related.