L14 - Drug action in the CNS - Antipsychotics

Question 1

Amine transmitters in the CNS

Answer 1

Noradrenaline
Dopamine
5-HT (Serotonin)
Acetylcholine

Question 2

How do anti-depressant drugs exert their action?

Answer 2

By interfering with amine transmission.

Question 3

What is the main area of action for noradrenaline?

Answer 3

The locus coeruleus, activity here increases with behavioural arousal, controlling wakefulness and alertness.

Question 4

Where are B1 receptors located in the brain and what do they do?

Answer 4

Located in the cortex , the hippocampus, and the striatum.
They contribute to the long-term effects of antidepressants.

Question 5

What are a2 receptors involved in?

Answer 5

Regulation of blood pressure, sedation and analgesia.

Question 6

What are a1 receptors involved in?

Answer 6

Involved in motor control cognition and fear.

Question 7

What is the main pathways of the action of dopamine?

Answer 7

1- The Nigrostriatal pathway - fine motor control
2- The Mesocortical and Mesolimbic Pathway - pleasure, reward/motivation, compulsion.
3- Tuber-hypophyseal - pituitary hormone secretion eg pituitary

Question 8

What is dopamine made from?

Answer 8

An amino acid called tyrosine, via the action of 2 enzymes.
- Tyrosine hydroxylase (rate limiting enzyme)
- DOPA (DOPA decarboxylase)

Question 9

How can we identify noradrenergic neurons?

Answer 9

Through the presence of B-hydroxylase.

Question 10

What are the different kinds of dopamine receptor?

Answer 10

D1 and D5 - Gs coupled receptors, stimulate adenylyl cyclase, increase cAMP, PKA and protein phosphorylation.
D2, D3 and D4 - Gi coupled receptors, inhibit adenylyl cyclase, activate potassium channels and oppose the effect of D1 receptor activation.

Question 11

Where are D2 receptors found?

Answer 11

In the pituitary gland and on DA neurones.

Question 12

How do cocaine and amphetamines effect DA and NA?

Answer 12

They increase their transmission,
They stimulate secretion, displace them from vesicles and cause reuptake transporters to work in reverse.

Question 13

What does increased DA signalling lead to?

Answer 13

increased motor activity

Question 14

What are amphetamine-like drugs used to treat?

Answer 14

Narcolepsy and attention deficit hyperactivity disorder (ADHD)

Question 15

What is schizophrenia?

Answer 15

a mental illness characterised by, disturbances in areas of the brain associated with thought, attention, motor behaviour and emotion.

Question 16

Symptoms of Schizophrenia?

Answer 16

Positive - Hallucinations, paranoid delusions, thought disorders, aggression.
Negative - blunting of emotions, social withdrawal, unresponsiveness, anhedonia.

Question 17

What causes schizophrenia?

Answer 17

It’s hereditary, a result of abnormalities that arise in early life
No single gene is responsible.
Consumption of cannabis in adolescence is one of the environmental factors.

Question 18

How are schizophrenic brains structurally different?

Answer 18

They have larger lateral ventricles and a smaller volume of tissue in the left temporal lobe.

Question 19

What drugs reduce the positive symptoms of SZ?

Answer 19

D2 blocking drugs (Antidopaminergics), while drugs that enhance DA signalling increase them.

Question 20

What does overactivity of the mesolimbic pathway contribute to?

Answer 20

Positive symptoms and increased D2 activity.

Question 21

What does underactivity of the mesocortical pathway contribute to?

Answer 21

Negative symptoms, D1 receptors are implicated.

Question 22

What is the dopamine theory of Schizophrenia?

Answer 22

1- Amphetamines produce behaviours similar to acute SZ episodes.
2- Hallucinations are a side effect of treating Parkinson’s patients.
3- DA release in animals produces stereotypical behaviours.
4- DA antagonists and drugs that block DA storage control positive symptoms and amphetamine induced behaviours.

Question 23

What are some unwanted side effects of taking antipsychotic drugs?

Answer 23

Parkinson’s like symptoms
Acute reversible dystonia
Increased prolactin release
Slowly developing irreversible tardive dyskinesia (involuntary movements.

Question 24

What are some new drug developments for SZ?

Answer 24

Drugs targeting glutamate (mGluR) Receptors