ADMET: Metabolism: Active Metabolites

Objective

Active metabolite:

A metabolite of an active drug that is also pharmacologically and therapeutically active

Objective

Pharmacophore

the 3-dimensional arrangement of moieties/functional groups that allow for specific drug-target binding

Why do we care about active metabolites?

because the presence of an active metabolite prolongs the effect(s) of a drug*

Binding to a drug target requires specific.... (3)

size, shape, and electronic distribution characteristics

Objective

an active metabolite is a metabolized version of a drug that maintains...

maintains enough of these characteristics (size, shape, electronic distribution) to still bind to the same drug target

Example: paliperidone is an active metabolite of risperidone

Example: desvenlafaxine succinate is an active metabolite of venlafaxine

Example: Nortriptyline an active metabolite of amitriptyline

Example: Desloratadine an active metabolite of loratidine

Example: Oxazepam an active metabolite of diazepam

Objective

Give an example, by either brand or generic name, of a currently-marketed drug that is also an active metabolite of another marketed drug

- desvenlafaxine active metabolite of venlafaxine

- nortriptyline active metabolite of amitriptyline

- desloratidine active metabolite of loratidine