L12 - Drug Action in the CNS - Anxiolytics I

Question 1

What is anxiety?

Answer 1

An antcipatory fear response, often independant of external events.

Question 2

What does the fear response give rise to?

Answer 2

Defensive behaviours
Autonomic reflexes
Alertness
Corticosteriod secretion
Negative emotions.

Question 3

What are some examples of anxiety disorders?

Answer 3

Social anxiety
Phobias
PTSD
OCD

Question 4

Describe the Elevated Plus Maze/ Cross Test?

Answer 4

One side of the cross is a barrier and the other is open.
Rodents are placed in the centre, woth the choice of walking through the closed or opened section.

Question 5

What is the main hypothesis from the Eleveated Maze/Cross Test in terms of anxiolytics?

Answer 5

The rodents would be afraid to go through the open area of the cross but after the anxiolytics they show no prefrence.

Question 6

Describe the Light/Dark box test

Answer 6

Rodents are given a choce of a light and dark side of a box to see what side they show preference for?

Question 7

What is the hypothesis for the Light/Dark box?

Answer 7

Rodents usuallly show preference for the dark side but after the anxiolytic are given the preference goes away.

Question 8

Do antidepressants cause a change in the fear response?

Answer 8

No

Question 9

What are GABAa receptors targets for?

Answer 9

Anxiolytics, hypnotics, anti-convulsant, neurosteroids and some general anaesthetics.

Question 10

What is GABA?

Answer 10

The main inhibitory neurotransmitter in the brain.

Question 11

GABAa Receptors…

Answer 11

• Their main role is to mediate inhibitory neurotransmission in the brain.
• Ionotropic receptors
• Chloride selective
• In the nicotinic superfamily
• made up of 5 subunits.

Question 12

What does activation of GABAa receptors lead to?

Answer 12

hyperpolarisation and reduction in excitability

Question 13

What is the agonist of GABAa at the orthosteric site?

Answer 13

Muscimol

Question 14

What is the competitive antagonist for GABAa?

Answer 14

Bicucuclline

Question 15

What is the non-competitive antagonist for GABAa?

Answer 15

Picrotoxin

Question 16

What is an agonist at the allosteric site for GABAa?

Answer 16

Benzodiazepines such as diazepam (an allosteric modulator)

Question 17

What is an allosteric modulator?

Answer 17

A substance that binds to a receptor to change that receptor’s response to stimulus.
They do not activate the receptor just changes the behaviour of the receptor when an agonist is bound.

Question 18

What is the antagonist at the allosteric site for GABAa?

Answer 18

Flumazemil

Question 19

What are some physiological effects of benzodiazepine agonists?

Answer 19

Sedation/anxiolytic effects
Hypnosis
Anterograde Amnesia
Anti-convulsant

Question 20

Benzodiazepines are…

Answer 20

Positive allosteric regulators of GABAa receptors, increasing activity.
They increase the chloride current across the membrane in the presence of GABA.

Question 21

How do benzodiazepines modulate GABAa receptors?

Answer 21

They increase their frequency of opening.

Question 22

How do barbiturates modulate GABAa receptors?

Answer 22

They increase the duration of opening.

Question 23

What do positive allosteric modulators (PAM) do?

Answer 23

Stabilises the receptor in state with increased affinity for GABA, this causes a leftward shift in the concentration response curve.

Question 24

What do negative allosteric modulators (NAM) do?

Answer 24

Stabilises the receptor in such a state that has reduced affinity for GABA and so remains closed/ harder to open.

Question 25

What determines benzodiazepines therapeutic uses?

Answer 25

Pharmacokinetics

Question 26

What are short acting compounds of benzos used as?

Answer 26

Sleeping pills

Question 27

What is intravenous diazepam used to treat?

Answer 27

Status epilepticus

Question 28

What is constitutive activity?

Answer 28

When GABAa receptor channels open in the absence of an agonist.

Question 29

What can reduce constitutive activity?

Answer 29

Inverse agonists