Psychodepressants Flashcards
Give some examples of Class A, B and C drugs
What are some of the most common drugs of abuse?
What are some examples of psychodepressants?
What receptors do they target?
*** Barbiturates (GABAA receptor)
* Benzodiazepines (GABAA receptor)
* GBL/GHB (GABAB receptor)
* Ketamine (NMDA receptor)
**
What type of channel does the GABAa receptor have?
What is the structure of the GABAa receptor?
o Pentameric
o Six alpha subtypes (a1-a6)
o Three beta subtypes (B1-B3)
o Three gamma subtypes (Y1-Y3)
o Also, delta, epsilon, Pi and omega subtypes
o 2a, 2b and Y are the most common organisation of GABAa receptor
o GABAa receptors are found pre-synaptically predominately
When is the GABA activity terminated?
GABA activity terminated upon reuptake by GABA reuptake transporter **GAT **
What are the multiple binding sites of the GABAa receptor?
o Agonist/ antagonist e.g., GABA
o Benzodiazepine binding site
o Channel blockers e.g., Picrotoxin
o Channel modulators e.g., GA
o Allosteric modulators e.g., Barbiturates
What effect do barbiturates have?
Positive allosteric modulator as they increase the functional response
What different neurotransmitter systems can barbiturates act on?
o Increase direct GABAA agonist
o Glycine receptor- also stabilises open channel
o nAChR and 5-HT3 receptor blockade
o AMPA/kainate blockade
o Blockade of Ca2+- dependent neurotransmitter release
**All increase inhibition (top 2) and decrease excitation (bottom 3) (check) **
BZD are cleaner but barbiturates have a higher risk of OD. What is the antidote if OD occurs by barbiturates?
No antidote
In medicine, what are barbiturates used for?
o Epilepsy
o General Anaesthetics
o Euthanasia
o Capital punishment (lethal injection)
How does Barbiturate addiction come about?
*** Tolerance **
o ‘Cold turkey’ and produce severe seizures- why?
Severe inhibition and excitatory imbalance due to neural adaptation to tolerance. So, if completely stopped taking barbiturate then imbalance would be extremely large causing seizures
o Unpleasant withdrawal > lack of pleasurable effect
o Previous symptoms are exacerbated due to neuroadaptation
Tell about benzodiazepines and where they are found?
- Positive allosteric modulators
- Between gamma and alpha interfaces of receptor
- GABA binding site stabilisation, increase GABA affinity
Do BZDs bind to all GABAa receptor alpha-gamma interfaces?
There are six subtypes of alpha (a1-a6)
The BZDs only bind to the a1, a2, a3 and a5 as they contain a **histidine residues **
Where as the a4 and a6 contain arginine residues
How do BZDs work to make the GABA binding site stable?
- Wobbling and oscillating between active and inactive form
- BZDs act as a stabiliser to receptor to be secure in open configuration allowing GABA to bind more easily than previously. This increases GABA affinity
How do BZDs work as a PAM?
- BZD acts as positive allosteric activity by increasing binding (green line above)
- Now need less GABA for response as affinity is greater
Tell me about the GABAb receptor
It inhibits propagation of AP by causing hyperpolarisation like GABAa
With the GABAb receptor, what equation can be used to calculate the K+ reversal potential?
The Nernst equation
What receptors does GBL/GHB target and what effect does it have?
What pathway does GBL/GHB target?
GHB addiction
What type of channel is the NMDA receptor?
What is the structure of the NMDA receptor?
What receptors do Ketamine/ PCP (similar compound to ketamine) target and how does it have its effect?
- Block channel from having ion flow
- NMDA on inhibitory cells –> activation –> GABA and other inhibitor NT (when activated)
- Low dose of ketamine causes more excitation than inhibition but at high dose this directly decreases excitation and causes depression
