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Glucuronidation of the OH-group at position 6, unlike that at position 3, does not affect affinity. The extent to which the 6-glucuronide contributes to the analgesic action remains uncertain at present. At any rate, the activity of this polar metabolite needs to be taken into account in renal insufficiency (lower dosage or longer dosing interval).
This isoenzyme breaks down dopamine in the corpus striatum and can be selectively inhibited by selegiline. Inactivation of norepinephrine, epinephrine, and 5-HT via MAOA is unaffected.


In contrast to drugs acting from the outside on cell membrane constituents, agents acting in the cellís interior need to penetrate the cell membrane. The cell membrane basically consists of a phospholipid bilayer (80A = 8 nm in thickness) in which are embedded proteins (integral membrane proteins, such as receptors and transport molecules).
Too rapid entry into the circulation would lead to unwanted systemic reactions such as: blockade of inhibitory CNS neurons, manifested by restlessness and seizures (countermeasure: injection of a benzodiazepine); general paralysis with respiratory arrest after higher concentrations.


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