In the treatment of Alzheimer's disease tacrine, a cholinesterase inhibitor, is 
not the drug of choice due to its low oral bioavailability, extensive hepatic 
first-pass effect, rapid clearance from the systemic circulation, pronounced 
hepatotoxicity, and the availability of drugs better than tacrine in the same 
pharmacological class. Hence, the aim of this investigation was to ascertain the 
possibility of direct nose-to-brain delivery of tacrine to improve 
bioavailability, to avoid the first-pass effect and to minimize hepatotoxicity. 
Tacrine solution (TS) in propylene glycol was radiolabelled with (99m)Tc 
(technetium) and administered in BALB/c mice intranasally (i.n.) and 
intravenously (i.v.). Drug concentrations in blood and brain were determined at 
predetermined time intervals post dosing. Drug targeting efficiency (DTE %) and 
the brain drug direct transport percentage (DTP %) were calculated to evaluate 
the brain targeting efficiency. Brain scintigraphy imaging in rabbits was 
performed to ascertain the uptake of the drug into the brain. Tacrine solution 
was effectively labelled with (99m)Tc and was found to be stable and suitable 
for in-vivo studies. Following intranasal administration tacrine was delivered 
quickly (T(max) 60 min) to the brain compared with intravenous administration 
(T(max) 120 min). The brain/blood ratios of the drug were found to be higher for 
[(99m)Tc]TS(i.n.) compared with [(99m)Tc]TS(i.v.) at all time points. The DTE 
(207.23%) and DTP (51.75%) following intranasal administration suggested that 
part of tacrine was directly transported to brain from the nasal cavity. Rabbit 
brain scintigraphy imaging showed higher uptake of the drug into the brain 
following intranasal administration compared with intravenous administration. 
The results showed that tacrine could be directly transported into the brain 
from the nasal cavity and intranasal administration resulted in higher 
bioavailability of drug with reduced distribution into non-targeted tissues. 
This selective localization of tacrine in the brain may be helpful in reducing 
dose, frequency of dosing and dose-dependent side effects, and may prove an 
interesting new approach in delivery of the drug to the brain for the treatment 
of Alzheimer's disease.