74
L. E. J. Kennis et al. / Bioorg. Med. Chem. Lett. 10 (2000) 71±74
In vivo, clonidine (0.04 mg/kg, s.c.) induced antidiar-
rhoeal action in male rats (200±250 g) challenged
simultaneously with castor oil (1 mL p.o.) was assessed
90 min after challenge.20 Test compounds or solvent
were administered 0.5 h before clonidine. Criterion for
drug-induced reversal; presence of diarrhoea (not
observed in controls; n ꢂ500). Reversal of the antidiar-
rhoeal eect of clonidine is obtained with a2-adreno-
ceptor blockers.
potent central in vivo activity in the xylazine test and
was therefore selected for further investigation.
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All of the compounds of Table 1 had high anities on
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22
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