M. Abe et Ki. Saito, REDUCTION OF WRAP RESTRAINT STRESS-INDUCED DEFECATION BY MKC-242, A NOVEL BENZODIOXAN DERIVATIVE, VIA 5-HT1A-RECEPTOR AGONIST ACTION IN RATS, Japanese Journal of Pharmacology, 77(3), 1998, pp. 211-217
Effects of MKC-242 odioxan-2-ylmethyl)amino]propoxy}-1,3-benzodioxole
HCl), a novel 5-HT1A-receptor agonist, and reference compounds on wrap
restraint stress-induced defecation were evaluated in rats. Wrapping
restraint stress increased defecation in rats. The increase was attenu
ated by putative 5-HT1A-receptor agonists, MKC-242 and 8-hydroxy-2-(di
-n-propylamino)tetralin (8-OH-DPAT). The suppressive effect of MKC-242
on wrap stress-induced defecation was antagonized by prior administra
tion of a 5-HT1A-receptor antagonist, WAY100135. MKC-242 did not affec
t spontaneous defecation and 5-HT-induced defecation. Diazepam and ami
triptyline also significantly reduced the stress-induced defecation. H
owever, amitriptyline showed a potent anti-cholinergic effect in the o
xotremorine-induced tremor test and reduced spontaneous defecation. In
contrast to MKC-242 and 8-OH-DPAT, buspirone and tandospirone tended
to suppress the increase at high doses. A major metabolite of buspiron
e and tandospirone, 1-(2-pyrimidinyl)piperazine, antagonized the suppr
essive effect of MKC-242. These findings suggest that stimulation of 5
-HT1A receptors reduces stress-induced defecation but not spontaneous
and 5-HT-induced defecation and that MKC-242 may be useful for the tre
atment of irritable bowel syndrome.