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Agonists can select for a1, a2, B1, B2, or non selectively bind to both B receptors.
Or, drugs can act indirectly: drug enters storage granule and displaces Norepi and some
dopamine. Most activity is seen at the B receptors.
Mixed agonists select for a1 receptors but demonstrate some results typical of B agonists
because they also act indirectly
a-2 receptor:
guanidine stucture
B-2 receptor:
- one or both of these structural modifications:
- t-butyl in place of isopropyl
- phenol or resorcinol instead of catechol
B-1 receptor:
- no specific SAR
Antagonists can select for a-1, B-1, or non-selectively bind to and block both B receptors.
There are no selective B-2 antagonists. One compound, phenoxybenzamine, selects for
both a-receptors. Two compounds, carvedilol and labetalol, block a-1, B-1, and B-2
receptors.
B-1 receptor:
- aryl group is a single benzene ring with a para-substitution of a heteroatom
(O,N, or S) containing, non-ionizable group
- O-CH2 present between aryl group and B-carbon
As a general rule, compounds with any OH on benzene rings will not cross blood brain
barrier due to ionization.
Metabolism
Adrenergic agonists and antagonists tend to be metabolized by COMT and MAO, which
shortens their half –life. Requirements for metabolism by these enzymes: