A. Kourounakis et al., SYNTHESIS AND EVALUATION OF BRAIN-TARGETED CHEMICAL DELIVERY SYSTEMS FOR THE NEUROTROPHOMODULATOR 4-METHYLCATECHOL, Journal of Pharmacy and Pharmacology, 49(1), 1997, pp. 1-9
Since various 4-alkylcatechols stimulate nerve growth factor (NGF) bio
synthesis both in-vitro and in-vivo, delivery of these agents to the b
rain may provide beneficial effect for the treatment of neurodegenerat
ive diseases such as Alzheimer's. Several dihydropyridine-pyridinium s
alt type redox chemical delivery systems (CDS) of 4-methylcatechol (4-
methylcatechol) were prepared as potential brain selective targetry fo
rms for 4-methylcatechol. After preliminary evaluation by in-vitro sta
bility studies in various buffer solutions and biological media, a sel
ected CDS was further investigated in the rat to determine its in-vivo
distribution. Selective and sustained delivery of the compound of int
erest to the rat brain was achieved. Furthermore, the NGF stimulatory
activity in the rat brain after peripheral administration of the selec
ted CDS was evaluated by measuring the levels of pre-pro-NGF mRNA in t
he rat hippocampus and frontal cortex, by dot blot hybridization and a
nalysis. Results showed the peripheral administration of the CDS to ac
hieve a 1.7-fold increase in NGF mRNA compared to control in the rat h
ippocampus, and an approximately 1.4-fold increase in the frontal cort
ex.