INTRANASAL ADMINISTRATION OF NEUROPEPTIDE-Y IN MAN - SYSTEMIC ABSORPTION AND FUNCTIONAL-EFFECTS

1 Exogenous neuropeptide Y (NPY, 10 nmol, 50 nmol and 100 nmol) and it s vehicle (NaCl 0.9%) were administered in a double blind, randomized and controlled manner by intranasal spray in 7 healthy volunteers. Var iations of plasma NPY concentration over time were measured during 120 min. Forty min after the administration of 50 nmol and 100 nmol of ex ogenous NPY, plasma NPY increased from 5.5+/-1.1 pM to 9.8+/-2.3 pM (P <0.05) and from 9.06+/-5.1 pM to 20.8+/-6.16 pM (P<0.001), respectivel y. There was no significant modification of the mean arterial blood pr essure and no subjective discomfort was reported. 2 Nasal airway resis tance (NAR) was measured by anterior rhinomanometry and was reduced by 25+/-3% and 32+/-5% after the spray of 50 nmol and 100 nmol, respecti vely, for about 90 min. 3 Double-blind, randomized, placebo-controlled and 3-way crossover design experiments were performed in 8 healthy vo lunteers to evaluate the influence of intranasal pretreatment with NPY (20 nmol) and the mixed alpha(1)/alpha(2)-adrenoceptor agonist oxymet azoline (20 nmol) on the functional effects of subsequent local irrita tion evoked by capsaicin (3.3 x 10(-4) mol). Subjective evaluation of NAR and local intensity of discomfort were evaluated by means of a vis ual analogue scale. Nasal secretions were collected and objective NAR was recorded by rhinomanometry. 4 Subjective NAR, nasal secretions and rhinomanometry recordings were not modified by intranasal application of saline, NPY or oxymetazoline. Subjective nasal obstruction, local discomfort, nasal secretions and NAR increase evoked by capsaicin were markedly reduced by NPY pretreatment (P<0.05) when compared to saline or oxymetazoline. 5 It is concluded that intranasal application of ex ogenous NPY has very low systemic absorption but induced long lasting nasal vasoconstriction without cardiovascular effects. Pretreatment of the nasal mucosa with exogenous NPY reduces both secretagogue and vas odilator responses to subsequent application of capsaicin.