V. Girard et al., PREJUNCTIONAL AND POSTJUNCTIONAL INHIBITORY EFFECTS OF FENSPIRIDE ON GUINEA-PIG BRONCHI, The European respiratory journal, 10(5), 1997, pp. 1015-1020
Fenspiride is a drug with potential benefits in the treatment of obstr
uctive airways disease. It has antibronchoconstriction and anti-inflam
matory properties, The aim of this study was to investigate the effect
of this drug on the contractions induced in the guinea-pig isolated m
ain bronchus and perfused lung by electrical field stimulation (EFS) o
r exogenously added agents. Bronchi were stimulated transmurally in th
e presence of indomethacin 10(-6) M and propranolol 10(-6) M, and isom
etric tension was measured. In the perfused lung model, calcitonin gen
e-related peptide (CGRP) release was determined in the perfusate fract
ions as a measure of neuropeptide production. Two successive contracti
le responses were observed: a rapid cholinergic contraction, followed
by a long-lasting contraction due to local release of neuropeptides fr
om C-fibre endings. Fenspiride (10(-6) to 10(-4) M) inhibited the nona
drenergic, noncholinergic (NANC) component of the contraction of the g
uinea-pig isolated main bronchus induced by EFS, Fenspiride significan
tly affected contractions induced by exogenously added substance P or
[Nle(10)]-NKA(4-10) only at concentrations higher than 10(-3) M. In th
e guinea-pig perfused lung, fenspiride inhibited low pH- but not capsa
icin-evoked release of CGRP, At higher concentrations (10(-4) M to 3x1
0(-4) M) fenspiride exhibited a significant inhibitory effect both on
the cholinergic component of contractile response induced by EFS in th
e guinea-pig isolated main bronchus and on exogenously added acetylcho
line. In conclusion, the result of this study suggests that fenspiride
, in moderate concentrations, reduces the release of neuropeptides, in
cluding tachykinins, from sensory nerve endings at a prejunctional lev
el. At higher concentrations, postjunctional actions on bronchial smoo
th muscle arp also present.