L12 - Drug Action in the CNS - Anxiolytics I Flashcards
What is anxiety?
An antcipatory fear response, often independant of external events.
What does the fear response give rise to?
Defensive behaviours
Autonomic reflexes
Alertness
Corticosteriod secretion
Negative emotions.
What are some examples of anxiety disorders?
Social anxiety
Phobias
PTSD
OCD
Describe the Elevated Plus Maze/ Cross Test?
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.
What is the main hypothesis from the Eleveated Maze/Cross Test in terms of anxiolytics?
The rodents would be afraid to go through the open area of the cross but after the anxiolytics they show no prefrence.
Describe the Light/Dark box test
Rodents are given a choce of a light and dark side of a box to see what side they show preference for?
What is the hypothesis for the Light/Dark box?
Rodents usuallly show preference for the dark side but after the anxiolytic are given the preference goes away.
Do antidepressants cause a change in the fear response?
No
What are GABAa receptors targets for?
Anxiolytics, hypnotics, anti-convulsant, neurosteroids and some general anaesthetics.
What is GABA?
The main inhibitory neurotransmitter in the brain.
GABAa Receptors…
- Their main role is to mediate inhibitory neurotransmission in the brain.
- Ionotropic receptors
- Chloride selective
- In the nicotinic superfamily
- made up of 5 subunits.
What does activation of GABAa receptors lead to?
hyperpolarisation and reduction in excitability
What is the agonist of GABAa at the orthosteric site?
Muscimol
What is the competitive antagonist for GABAa?
Bicucuclline
What is the non-competitive antagonist for GABAa?
Picrotoxin
What is an agonist at the allosteric site for GABAa?
Benzodiazepines such as diazepam (an allosteric modulator)
What is an allosteric modulator?
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.
What is the antagonist at the allosteric site for GABAa?
Flumazemil
What are some physiological effects of benzodiazepine agonists?
Sedation/anxiolytic effects
Hypnosis
Anterograde Amnesia
Anti-convulsant
Benzodiazepines are…
Positive allosteric regulators of GABAa receptors, increasing activity.
They increase the chloride current across the membrane in the presence of GABA.
How do benzodiazepines modulate GABAa receptors?
They increase their frequency of opening.
How do barbiturates modulate GABAa receptors?
They increase the duration of opening.
What do positive allosteric modulators (PAM) do?
Stabilises the receptor in state with increased affinity for GABA, this causes a leftward shift in the concentration response curve.
What do negative allosteric modulators (NAM) do?
Stabilises the receptor in such a state that has reduced affinity for GABA and so remains closed/ harder to open.
What determines benzodiazepines therapeutic uses?
Pharmacokinetics
What are short acting compounds of benzos used as?
Sleeping pills
What is intravenous diazepam used to treat?
Status epilepticus
What is constitutive activity?
When GABAa receptor channels open in the absence of an agonist.
What can reduce constitutive activity?
Inverse agonists
