Js. Lacroix et al., INTRANASAL ADMINISTRATION OF NEUROPEPTIDE-Y IN MAN - SYSTEMIC ABSORPTION AND FUNCTIONAL-EFFECTS, British Journal of Pharmacology, 118(8), 1996, pp. 2079-2084
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.