Chemistry And Structureactivity Relationships Noncovalent Inhibitors

These agents share mechanism (above and Figure 8-1) but differ in their disposition in the body and their affinity for the enzyme. Edrophonium, a quaternary drug whose activity is limited to peripheral nervous system synapses, has a moderate affinity for AChE. Its volume of distribution is limited and renal elimination is rapid, accounting for its short duration of action. By contrast, tacrine and donepezil (Figure 8-2) have higher affinities for AChE and are more hydrophobic, contributing to their longer durations of action; they readily cross the blood-brain barrier to inhibit AChE in the central nervous system (CNS).

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