AUTONOMIC NERVOUS SYSTEM DRUGS

tyrosine

tyrosine hydroxylase

converts tyrosine to levodopa

levodopa

DOPA decarboxylase

converts levodopa to dopamine

dopamine

dopamine B-hydroxylase

converts dopamine to norepinephrine

epinephrine

norepinephrine

N-methyl transferase

converts norepinephrine to epinephrine

1. phenylethylamine

2. catechol ring

3. B-hydroxyl

essential SAR of adrenergic drugs

3-OH

adrenergic SAR: phenyl substituent required for direct alpha binding activity

4-OH

Adrenergic SAR: Phenyl substituent required for direct $\beta$ binding activity

susceptibility to COMT metabolism

Metabolic consequence of having both 3-OH and 4-OH groups on the phenyl ring

increased lipophilicity

Effect on lipophilicity when both ring OH groups are absent

longer DOA

Duration of Action (DOA) implication of lacking both ring OH groups