Structure-Activity Relationship (SAR) Of Sympathomimetic Agents

• Structure-Activity Relationship mimic catecholamines (epinephrine, norepinephrine, dopamine) by stimulating adrenergic receptors (α and β).
• Their activity depends on structural modifications affecting receptor selectivity, metabolism, and CNS penetration.

Key Structure-Activity Relationship Features

1. Catechol Ring Substitutions

   • 3,4-Dihydroxy (Catechol): High α/β activity, rapid metabolism (e.g., Epinephrine, Norepinephrine).
   • Single Hydroxyl (-OH) Group: Reduces metabolism, increases α1 selectivity (e.g., Phenylephrine).
   • No -OH Groups: Poor COMT metabolism, better CNS penetration (e.g., Amphetamine, Ephedrine).

2. Amine Group Substitutions

   • Small groups (-H, -CH3): Preferential α-receptor activity (e.g., Norepinephrine).
   • Bulky groups (-CH(CH3)2, -C(CH3)3): Enhanced β-selectivity (e.g., Isoproterenol, Albuterol).

3. Alpha-Carbon (-CH3) Substitution

   • Inhibits MAO metabolism, prolongs duration, increases CNS effects (e.g., Ephedrine, Amphetamine).

4. Beta-Hydroxyl Group (-OH at β-carbon)

   • Present: Strong receptor binding, reduced CNS penetration (e.g., Epinephrine).
   • Absent: Increased CNS activity, indirect action (e.g., Amphetamine).

Classification Based on SAR

• Direct-Acting: Epinephrine (α/β), Phenylephrine (α1), Albuterol (β2).
• Indirect-Acting: Amphetamine, Tyramine, Cocaine.
• Mixed-Acting: Ephedrine, Pseudoephedrine.

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