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A series of N-(aminoiminomethyl)-1H-pyrrole-1-acetamides, related to guanfacine, were prepared and tested for antidiarrheal activity in castor oil dosed rats. trans-N-(Aminoiminomethyl)-2,5-dihydro-2,5-dimethyl-1H-pyrrole-1-acetami de (2), in which the dichlorophenyl ring of guanfacine is replaced by 2,5-dimethyl-2,5-dihydropyrrole, showed potent antidiarrheal activity but possessed only minimal cardiovascular activity in rats.

A grease-gap extracellular recording technique was used to detect 5-HT1A receptor-mediated hyperpolarizing responses to 5-hydroxytryptamine (5-HT) in the rat isolated superior cervical ganglion. In the presence of the novel 5-HT1A receptor antagonist, WAY-100135 [N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropan amide], the responses to 5-HT were antagonised in a competitive manner with a pA2 value of 7.2 (6.9-8.5) and Schild plot slope of 1.0 (0.4-1.6), n = 20. The antagonist activity was greater in the (+) than the (-)enantiomer of WAY-100135. The pA2 value of the (+)enantiomer was 7.5 (7.2-8.0), Schild plot slope 1.2 (0.8-1.6), n = 17. In contrast the (-)enantiomer had weak antagonist activity (pA2 6.3 +/- 0.25, n = 3). No agonist activity of WAY-100135 or its enantiomers were observed in this study.

Dargestellt und auf Wirkung gegen Diarrhoe untersucht werden die Verbindungen (II)‐(IV).