beta blockers Flashcards
what is responsible for the flight or flight response?
adrenaline
what is the difference between adrenaline and no adrenaline- structurly?
difference of methyl group
what is the pre-cursor of adrenaline?
L-tyrosine
what are the adrenaline endogenous agonists?
adrenaline, noradrenaline ad catechol ring system
what kind of biosynthesis does adrenaline have?
transferase reaction- primary to secondary reaction
what is the sequence in the adrenaline biosynthesis?
l tyrosine>levodopa
>dopamine>na>ad
what are the recognition motifs of beta blockers
TM6 - asparagine residue (OH + Phe pi-stacking)
TM5 - 2 serine residues (phenol OH’s)
TM3 - aspartate residues (amine)
why may there be a lysozyme attached to a b-adrenoreceptor?
to aid crystallisation
what structure is a b-adrenoceptor
g-protein coupled receptor
7 transmembrane helix
what happens in the B-adrenoceptor binding site?
non-covalent interactions
h bond with alcohol
pi stacking with 6 transmembrane helix with benzene ring
agonsist must have pair of 204 and 207 catechol
How were 3rd generation BB made and examples
By adding chain extensions. Ex. Epanolol, Primidilol, Xamoterol
what happens when you add isoprenaline?
makes it selective for beta
what has a bigger hydrophobic pocket, alpha or beta?
beta
what is the difference between agonists and antagonists?
Agonists bind to receptors causing physiologocial effects. Antagonists are usually more spread out and work by removing the main binding groups
how do you improve antagonism?
spreading out the binding groups
how was the first antagonist made?
adding 2nd aromatic ring
what the problem with first generation drugs crossing the BBB
cause reactions in CNS kike dizziness and sedation. Caused bronchoconstriction in people with asthma
Making gen 2 BB
how did we get selectivity between beta 1 and beta 2 receptors
- Increase polarity so it cant pass BBB by adding functional groups
- extra H-bonding interactions and para substitutions instead if meta
what are 3rd gen bb?
extra lipophilic interactions- extra H bonding
what are BB’s?
they are antagonists of B-adrenoceptors
what reduces agonism?
replacing catechol unit with naphthalene
