W. Jiang et D. Grundy, Modulation of gastrointestinal afferent sensitivity by a novel substitutedbenzamide (ecabapide), J AUTON NER, 78(2-3), 2000, pp. 99-108
The effects of ecabapide, a novel substituted benzamide compound (3-[2-(3,3
-dimethoxyphenyl)ethylcarbamoylmethyl]methylbenzamide) that has gastrointes
tinal prokinetic action, were examined on the discharge of extrinsic affere
nt nerves supplying the stomach and jejunum in anaesthetized rats. Ecabapid
e (60 and 180 mu g kg(-1), iv) had no effect on the baseline discharge of v
agal gastric distension-sensitive afferents or the stimulus-response profil
e to gastric distension. Ecabapide also had no effect on either spontaneous
jejunal mesenteric afferent nerve discharge or responses to intestinal dis
tension. Ecabapide (180 mu g kg(-1)) significantly inhibited the maximum di
scharge of jejunal afferents induced by cholecystokinin (CCK8; 50 pmol, iv)
, whereas it failed to inhibit the excitatory action of 2-methyl-5-hydroxyt
ryptamine (2Me-5-HT; 10 mu g, iv), a selective 5-HT3 receptor agonist. A mo
del of acute focal intestinal ischaemia was used to evaluate the actions of
ecabapide on the discharge of activated jejunal afferents. Ischaemia produ
ced a substantial increase in afferent discharge which was reproducible whe
n the duration of ischaemia was limited to less than 10 min and repeated ev
ery 15 min. Ecabapide at doses of 60 and 180 mu g kg(-1) significantly redu
ced ischaemia-induced increases in afferent discharge. In addition to its t
herapeutic efficacy as a gastrointestinal prokinetic agent, these findings
show also that ecabapide may also have an inhibitory action on the discharg
e of intestinal afferents activated by ischaemia. (C) 2000 Elsevier Science
B.V. All rights reserved.