Abstract:
The unique anatomical arrangement of blood vessels and sinuses in the human skull and the brain, the prevalence
of a high density of skin appendages in the scalp, extracranial vessels of the scalp communicating with the brain
via emissary veins and most importantly, the way that the scalp is used in Ayurvedic medical system in treating
diseases associated with the brain show that a drug could be transcranlaUy delivered targeted to the brain through
the scalp. The present study was to investigate by measuring the antinociceptive effect on rats whether the opioid
analgesic methadone could be delivered targeted to the brain by transcranial delivery route. A non aqueous solution
of methadone base in sesame oil was used for the application on the scalp. Animal studies were carried out using
six groups of male rats consisting of group 1, the oral control treated with distilled water I mi; group 2, the oral
positive control tr^ted with methadone hydrochloride solution 316.5 pg/ml; group 3, the negative control treated
transctanially with the blank sesame oil 0.2 ml and three test groups 4, 5 and 6 treated with three different dose
levels of the transcranial oil formulation of methadone base, 41.6 pg/0.2 ml, 104 pg/0.2 ml and 208 }ig/0.2 ml,
respectively. The antinociceptive effects were examined by subjecting the rats to the hot plate and tail flick tests. The
two higher concentrations of the three transcranial methadone formulations yielded response vs rime curves showing
nearly equal maximimi antinociceprive effects similar to that of the oral positive control. Maximiun analgesic effect
after transcranial admirustrarion was observed between 1st and 2nd h and declined up to 6th hour. The results
indicate that the transcranial brain targeted delivery of methadone base in the form of an oil based non aqueous
solurion results in statistically significant antinociceptive effects under experimental conditions. Therefore, it is
possible to deliver central nervous system drugs through tlie proposed transcranial route when suitably formulated.
