Lecture 3 - Neuropharmacology

Question 1

What are the symptoms of depression?

Answer 1

Anhedonia
Sustained bad mood
Low serotonin –. bad mood
Low NA –> low drive

Question 2

What is anhedonia?

Answer 2

the inability to feel pleasure in normally pleasurable activites

Question 3

What are the key anti-depressants also used as anxiolytics?

Answer 3

Tricyclics
SSRIs
SNRIs
MAOIs

Question 4

How do tric-cyclics work?

Answer 4

They inhibit NA and 5HT reuptake therefore increasing the synaptic concentration of both.

Question 5

Give an example tri-cyclic

Answer 5

Amoxapine

Question 6

How do SSRIs work?

Answer 6

They inhibit 5HT reuptake –> Increased synaptic serotonin

Question 7

Give an example of an SSRI

Answer 7

Citalopram

Question 8

How do MAOIs work?

Answer 8

They inhibit monoamine oxidase leading to increased synaptic NA and 5HT concentrations

Question 9

Give an example MAOI

Answer 9

moclobemide

Question 10

How do SNRIs work?

Answer 10

They inhibit both NA and 5HT reuptake thus increasing synaptic concentrations of NA and 5HT
Higher efficacy than try-cyclics

Question 11

Give an example SNRI

Answer 11

Venlafaxine

Question 12

How come the results of anti-depressants/anxiolytics can take weeks-months?

Answer 12

An increase in synaptic NA and 5HT causes increases neurogenesis int he dentate gyrus, increase in dendrite arborisation and synaptogensis and pre-synaptic desenstization

Question 13

What is the key problem with developing new anti-depressants and anxiolytics?

Answer 13

There is a huge placebo effect

Question 14

What are promising new targets for anti-depressant development?

Answer 14

Sodium dependent serotonin transporter and the noradrenine transporter
Opoid receptors
NMDA receptors
mGluR5
mGluR7

Question 15

Outline the process of validating a new drug target for emotional disorders

Answer 15

Is it localised in key areas?
Perform genetic studies: ablation, KO
Use agonists and antagonists
Drug screening for suitable antagonists

Question 16

What are the patterns of communication in the nervous system?

Answer 16

Point to point

Diffuse modulatory

Question 17

What NTs does Point to point communication use?

Answer 17

Glu and GABA

Question 18

Outline diffuse modulatory communication

Answer 18

Key in anxiety and depression
NA - controls attention, drive, arusal and sleep wake
5Ht - controls mood

Question 19

What disease is the cholinergic diffuse modulatory system important in?

Answer 19

Alzheimer’s Disease

Question 20

What are the drugs currently marketed for AD and how do they work?

Answer 20

Exelon and Ancept target acetylcolinesterase causing an increase in ACh in the CNS compensating for degeneration

Question 21

What are the problems with Exelon and Ancept, the AD drugs?

Answer 21

They have a low efficacy and many side effects

Question 22

What disease is the dopaminergic diffuse modulatory system important in?

Answer 22

Parkinson’s Disease

Question 23

What is important about the dorsal dopaminergic diffuse modulatory system?

Answer 23

It is key for movement initiation

Question 24

What is important about the ventral dopaminergic diffuse modulatory system?

Answer 24

Involved in cognition, reward and addiction

Question 25

What are the positive symptoms of schizophrenia?

Answer 25

Delusions Hallucinations

Question 26

What are the negative symptoms of schizophrenia?

Answer 26

Lack of emotion Low energy Social isolation

Question 27

When is the typical onset of schizophrenia?

Answer 27

Late puberty

Question 28

What are the main anti-psychotics?

Answer 28

Chlorpromazine Haloperidol Atypical Anti-psychotics

Question 29

Describe Chlorpromazine, the anti-psychotic

Answer 29

D2 receptor antagonist | Causes sleepiness, weight gain, tardive dyskinesia

Question 30

Describe the anti-psychotic Haloperidol

Answer 30

Can cause EPS | D2 receptor antagonist

Question 31

What is EPS?

Answer 31

Extra pyramidal symptoms including dystonia, akathasia, parkisonisn and tardive dyskinesia

Question 32

Name two atypical anti-psychotics

Answer 32

Clozapine andOlanzapine

Question 33

Describe atypical anti-psychotics

Answer 33

Very high affinity for the D4 receptor EPS is reduced Prolonged high dose causes destruction of organs High efficacy

Question 34

What is PCP?

Answer 34

A street drug that induces the positive symptoms of schizophrenia, enhances psychosis in patients with Schizophrenia by blocking NMDA receptors

Question 35

Outline a new possible method of treating Schizophrenia

Answer 35

Using mGlu2/3 receptors agonists No EPS Symptoms Showed improvement of both positive and negative symptoms compared to Olanzapine In rats induced epileptic seizures, not seen in humans

Question 36

What is the Best reward pathway?

Answer 36

The Frontal Dopamine Diffuse modulatory system

Question 37

How does nicotine work?

Answer 37

It targets alpha 7 causing increased cognition

Question 38

How do amphetamines work?

Answer 38

They increase NA, DA and 5HT by blocking reuptake and facilitating release

Question 39

How does cocaine work?

Answer 39

Increases DA, NA and 5HT by blocking reuptake

Question 40

How does cannabis work?

Answer 40

It targets the CB1 receptor

Question 41

How does ethanol work?

Answer 41

It targets the GABA a receptor causing increased function, acting as an anxiolytic and sedative It increases DA and L glu release

Question 42

What is important about mGluR7?

Answer 42

It is a possible target for treating alcohol dependence, as agonists reduce alcohol consumption

Question 43

How does LSD 25 work?

Answer 43

It increases efficacy of psychoanalysis