Blood Brain Barrier

Question 1

How is the brain protected and nourished

Answer 1

Skull and vertebral column
The meninges (protective membranes)
Cerebrospinal fluid (cushioning)
BBB (highly selective- limits blood access

Question 2

What is the meninges

Answer 2

an outer protection for the brain
3 layers
dura mater (strong)
arachnoid mater (vascular)
pia mater (gentle/ thin)

Question 3

What are the routes of drug absorption across Mucosae

Answer 3

Transcellular lipophilic pathway
Carried Mediated Transport
Receptor Mediated transcytosis

Question 4

How can you engineer drugs to use carrier mediated transport?

Answer 4

Couple to L-cysteine (small neutral AA with low affinity for LAT1)
This creates a greater affinity for LAT1

Question 5

What is LAT1

Answer 5

Transporter in the brain Large Neutral Amino acid Transporter 1

Question 6

How are small molecules transported via lipid mediated transport

Answer 6

Need to be less than 400MW highly lipid soluble
CNS active drugs need less than 7 H-bonds
BBB permeation decreases 100x from increasing MW from 300 to 450

Question 7

What is carrier mediated transport

Answer 7

Where drug molecules are adapted to increase affinity for endogenous transporters
Part of the drug acts as a carrier for the drug itself to be taken up by many transporters