Learning Objective

By the end of this note, the learner should be able to distinguish drug actions that occur via enzyme inhibition from those that occur via transporter inhibition.

Enzyme-Linked Drug Actions

Many drugs exert their effects by inhibiting enzymes. This stops the enzyme from converting its substrate into its product, leading to the buildup or depletion of certain molecules.

Examples of Enzyme Inhibition

• Acetylcholinesterase inhibitors
  (e.g., donepezil, neostigmine) → ↑ ACh
• Angiotensin-converting enzyme (ACE) inhibitors
  (e.g., lisinopril) → ↓ Ang II
• HIV aspartate protease inhibitors
  (e.g., ritonavir)
• Carbonic anhydrase inhibitors
  (e.g., acetazolamide)
• Cyclooxygenase (COX-1 & COX-2) inhibitors
  (e.g., NSAIDs)
• Dihydrofolate reductase inhibitors
  (methotrexate, trimethoprim)
• Viral DNA/RNA polymerase inhibitors
  (e.g., acyclovir, remdesivir)
• Monoamine oxidase inhibitors (MAOIs)
  (e.g., phenelzine)
• Na⁺/K⁺-ATPase inhibitors
  (e.g., digoxin)
• Neuraminidase inhibitors
  (e.g., oseltamivir)
• Reverse transcriptase inhibitors
  (zidovudine, tenofovir)

Transporter-Linked Drug Actions

Some drugs act on membrane transporters, not receptors or enzymes. Transporters control the reuptake of neurotransmitters.

High-Yield Transporter Inhibitors

• Dopamine transporter (DAT) inhibitors
  (e.g., cocaine, methylphenidate)
• Norepinephrine transporter (NET) inhibitors
  (e.g., TCAs, SNRIs)
• Serotonin transporter (SERT) inhibitors
  (e.g., SSRIs like fluoxetine)
• GABA reuptake inhibitors
  (e.g., tiagabine)

These drugs increase neurotransmitter concentration in the synaptic cleft.

Activity