Lecture 10 (The Adrenergic System 2) Flashcards
What is B1 receptor agonist used for clinically?
increase HR and force of contraction
*used for acute heart failure or decreased CO that may occur after surgery
What is B2 receptor agonist used for clinically?
- bronchodilation of lungs
- relaxation of uterus
- useful for treatment of asthma and COPD
- used to prevent premature labor
Most of therapeutically used B agonists are ?
secondary amines
Majority of B agonists are ?
phenylethylamines
Do any imidazolines act as B agonists?
no
*this is another indication that the imidazolines are only alpha agonists
imidazolines are always _____ agonists
alpha
As R on the B adrenergic agonist increases. what happens?
generally affinity increases for B receptors
Why does the N need to be charged?
for receptor binding
What is the H bond on the OH on B more important for?
more important for B2 receptor binding
not needed for B1 receptor binding
Large R substituents on the N do what for alpha receptors?
- decrease intrinsic activity at alpha 1 and alpha 2 receptors
- but affinity increases as R gets very large
Large R substituents on the N do what for beta receptors?
-increases affinity for B1 and B2 receptors while keeping intrinsic activity the same or increasing it
isopropyl selective for?
B1 and B2 > alpha
t-butyl selective for?
B2 > B1
A methyl group on (alpha or 2) does what?
selective for alpha 2
but a methyl or ethyl group also increases B2 affinity over B1
An OH on (B or 1) is important for ?
it is more important for B2 affinity than B1
What does R1 ring substituents do?
usually consists of 2 substitutions capable of forming H-bonds (donor or acceptor)
*anything less tends to reduce B2 and B1 affinity
What does an N-ethylphenol group do?
increases both affinity and intrinsic activity at B2 receptors.
What do large hydrophobic 7-11 atom long chains do?
also increases affinity and activity at B2 receptors while prolonging duration
Describe the two B2 receptor binding sites
1) the nearest site to the N accommodates a t-butyl group
and distal to this
2) is a hydrophobic binding pocket that also seems to require a phenolic OH for optimal binding or a longer hydrophobic chain
N-isopropyl does what?
-produces the highest intrinsic activity for B1 receptors
- has affinity for B1 and B2 receptors
- low affinity and activity for alpha 1 or alpha 2
What is isoproterenol used for?
has limited use as a bronchodilator because it has cardiac stimulatory activities conferred by B1 receptors binding
How does isoproterenol decrease vascular resistance?
- causes vasodilation in muscular blood vessels
- increases CO (HR and SV) and force of contraction.
Absence of OH on a b1-receptor agonist does what?
makes it more selective for B1 than B2
What group produces the highest intrinsic activity for B1 receptors?
N-isopropyl
