The aim of the study was mainly to investigate the relationship between concentration of rivastigmine and its
inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) following intranasal (IN) and intravenous
(IV) administration in rats, and to provide a novel nasal delivery route for the brain disease therapy. Rivastigmine was
administered to male rats at 2 mg/kg by IN and IV route. Drug concentration, AChE and BuChE activity were measured
in the plasma, central nervous system (CNS) regions i.e. olfactory region, hippocampus, cerebrum and cerebellum, and
peripheral tissues. It was determined that rivastigmine was characterized by extremely rapid and complete absorption into
the systemic circulation followed by a rapid decline in the plasma concentrations, and can also quickly distribute into CNS
and peripheral tissues by the two routes. IN administration showed higher concentration in CNS regions and longer action
on inhibiting the activity of AChE and BuChE than IV administration. More significant decrease of the two enzymes was
observed in CNS regions than in peripheral tissues for both administrations. A close relationship was found between the
concentration of rivastigmine and enzyme inhibition in plasma and CNS tissues in rats. Based on these findings, it was
concluded that rivastigmine could cause relatively strong inhibition of AChE and BuChE in plasma and brain tissues, especially
in hippocampus, cortex and cerebrum. The pharmacodynamics was closely related to its concentration in vivo.
The intranasal route can be strategy for delivering the drug into brain.