this lecture talks about the the chemical activity of adrenergic receptor antagonist drugs , SAR , MOA , uses , side effect . adrenergic receptor antagonists (also called alpha-blockers) are a family of agents that bind to and inhibit type 1 alpha-adrenergic receptors and thus inhibit smooth muscle contraction. Their major uses are for hypertension and for symptomatic benign prostatic

1. ADRINERGIC
ANTAGONISTS
DR . FAHD NAIF

2. Clinical uses:
Anti-hypertensive.
To treat cardiac failure.
To control urinary output.
In prostatic hyperplasia.

3.  They have diverse structural features compared to
catecholamines.
 They will block adrenergic receptors preventing
catecholamines from exerting their actions.
 The binding is reversible in almost all cases.

5.  Mainly limited to selective 1 antagonists.

6.  Mainly limited to selective 1 antagonists.
 Used as anti-hypertensive and in benign prostatic
hyperplasia.
 Prazocin is short acting while terazocin and
doxazocin are longer acting (Why?)

8.  2 receptors are presynaptic... Activation leads to
decrease in N.A release.
 They are used as anti-depressant agents (depression is
associated with a decrease in N.A and serotonin
levels).

9.  β-blockers:
 The clinically used ones are β1-blockers.
 Clinical effects:
 Reduce cardiac output.
 Reduce rennin release from the kidney… reduce angiotensin I
formation which is the precursor for angiotensin II (a potent
vasoconstrictor).
 Clinical uses:
 in hypertension.
 Angina.

10.  Broncho-constriction… not recommended in asthmatic
patients.
 Fatigue and tiredness in limbs due to reduced cardiac
output.
 CNS s/e…. Mainly for lipophilic agents.

11.  Isopreterenol was used as a lead for the synthesis of new
selective β1-blockers although it is a β2-agonist.
 The structure was studied to convert the agonist activity
to antagonist effect.

13. Branched alkyl groups are
Good for antagonist activity
Important for ionic bonding
Important for H-bonding
Substitutions lower activity
Important for H-bonding
Important for hydrophobic interactions

14. Branched alkyl groups are
Good for antagonist activity
Important for ionic bonding
Important for H-bonding
Substitutions lower activity
Important for H-bonding
Important for hydrophobic interactions

16. Amide group should be at P position for
good binding to the receptors

17. Possible Hydrophobic
interaction
Possible H-bond
interaction

19.  Have extended alkyl side chain attached to the amino group bearing
moiety capable for H-bonding.

20. The End