BENZODIAZEPINE

Question 1

Features of GABA receptors

Answer 1

1. Subunit has 4 domains
2. gaba has 5 subunits
3. GABA A receptors activate Cl ions
   When an action potential is firing, GABA is released into the synapse = where it acts at GABA-A receptors

Question 2

SAR of BDZ

Answer 2

1. Cl binding prevents binding to CNS
2. Nitro binding helps anticonvulsant actions
3. Fluorine promotes sedative, hypnotic action
4. Metabolism introduces an OH (on diazepine nucleus
5. Another ring structure onto may produce CNS antagonism

Bdz Are not selective full agonists

Question 3

Benzodiazepine nucleus

Answer 3

Question 4

Binding sites of BDZ

Answer 4

• 2 GABA binding sites at the beta-alpha interface
• BDZ bind at interface between alpha and gamma2 subunits

Question 5

Which subunits are BDZ sensitive?

Answer 5

Alpha1, 2, 3 and 5

Question 6

Which GABA A Receptor subtypes are insensitive

Answer 6

alpha 4 and 6

Question 7

Therapeutic actions of the following alpha subunit

Answer 7

Alpha 1 = sedation

Alpha 2 = anxiolytic

Alpha 3 = same as 2, but Higher

Alpha 5 = learning and memory

Question 8

Where do NON BDZ HYPNOTICS BIND?
Zolpidem and zopiclone

Answer 8

Same as BDZ

Question 9

Does zolpidem have some subtype selectivity?

Answer 9

Yes.
Bind Highly to a-1
Then at a2/3
Not much at a5

Question 10

Is zolpiclone selective?

Answer 10

No.
Non selective for a1-3,5 containing receptors

Question 11

Short acting BDZ …
ATOM

Answer 11

Alprazolam
Triazolam
Oxazepam
Midazolam

Question 12

Intermediate acting BDZ
THIN LAYER CHROMOGRAPHY
TLC

Answer 12

Temazepam
Lorazepam
Clonazepam

Question 13

Long acting BDZ

…CDeF..

Answer 13

Clorazepine
Clordiazepoxide
Diazepam
Flurazepam

Question 14

BDZ
NOT MET IN LIVER

OTL
OUT THE LIVER

Answer 14

Oxazepam
Temazepam
Lorazepam