Question

When looking at an active metabolite of a medication, such as 9-hydroxyrisperidone (paliperidone), how does it differ from the parent compound in terms of lipophilicity?

Answer 1

Paliperidone has low affinity for lipid-rich environments compared from the parent compound risperidone. Due to its hydrophilicity characteristic, paliperidone is capable of hydrogen bonding with other molecules containing water and hydroxyl groups. Lipophilicity is a determining factor for the rate and degree of metabolism of the drug in the body and for crossing the blood–brain barrier (BBB).

Moreover, these differences are implicated in synaptic plasticity and neuronal firing effects in the mechanism of mitochondrial movement, protein expression, and phosphorylation of the drug. Paliperidone as a mood stabilizer is an active metabolite of risperidone with antipsychotic effects used for the treatment of schizophrenia and its associated disorders.