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 transcranially delivered and 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 and 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 1 ml; group 2, the oral positive control treated with methadone hydrochloride solution 316.5 μg/ml; group 3, the negative control treated transcranially 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 μg/0.2 ml, 104 μg/0.2 ml and 208 μg/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 time curves showing nearly equal maximum antinociceptive effects similar to that of the oral positive control. Maximum analgesic effect after transcranial administration 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 solution results in statistically significant antinociceptive effects under experimental conditions. Therefore, it is possible to deliver central nervous system drugs through the proposed transcranial route when suitably formulated.

Introduction: IL−13 is a Th2 cytokine that has a potential pivotal role in allergic and asthmatic responses, including airway remodelling. Our objective was to evaluate the effects of anti−IL−13 on the inflammatory response following repetitive NAC in seasonal allergic rhinitis. Study design: A parallel group double−blind placebo−controlled study (n=16 and 15) with an open label group given topical nasal corticosteroids (n=5). Subjects received intranasal Timothy grass pollen (Phleum P5 allergen), and serial samples were taken using Synthetic Absorptive Matrix (Accuwik Ultra) and by nasal lavage. NAC was performed at screening and on days 5, 6 and 7 following infusion of anti−IL−13 or placebo. Results: Anti−IL−13 was found to profoundly inhibit levels of IL−13, and to a lesser extent eotaxin in SAM eluates during the late phase after NAC. However, there were no apparent effects on levels of nasal lavage eosinophils nor nasal symptom scores. In contrast, topical nasal corticosteroid caused pronounced suppression of IL−13, IL−5 and eotaxin in the late phase, inhibited the levels of lavage eosinophils, and decreased symptom scores in the late phase. Conclusions: Anti−IL−13 has specific pharmacodynamic target action, causing profound inhibition of nasal IL−13 responses. However, failure to inhibit nasal symptoms and eosinophils, suggests anti−IL−13 is not critical to the acute nasal allergic response. Further studies are now required to assess the effects of anti−IL−13 in asthma; and especially to elucidate effects on the airways in terms of inflammation, hyperreactivity and remodelling. This abstract is funded by: Novartis Pharmaceuticals.

Sublingual immunotherapy (SLIT) is now an established treatment for allergic rhinitis. Whilst several systematic reviews have now confirmed clinical efficacy and safety, recent analysis also confirms that therapeutic benefit persists for several years after the com- pletion of SLIT. Such findings, along with the obvious ease of administration of sublingual preparations, have clearly promoted SLIT as an attractive option for treatment of allergic rhinitis resistant to medical treatment. This article reviews the development, efficacy and safety of SLIT in allergic rhinitis and the current indications for its use.

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