Abstract:
:New 2-piperazinylbenzothiazole and 2-piperazinylbenzoxazole derivatives were prepared and tested as 5-HT3 receptor antagonists. Some of the new compounds antagonized the effect of 5-HT at the longitudinal muscle myenteric plexus (LMMP) preparation of the guinea pig ileum, and two benzothiazole derivatives, compounds 2e and 2f, were more potent than ondansetron in this regard. However, these two compounds were much weaker than the typical 5-HT3 receptor antagonist as displacers of [3H]BRL-43694 binding to rat cerebral cortex homogenates or as antagonists of the bradycardia response to 5-HT in the anaesthetized rat. Like the prokinetic agent cisapride, some of the new compounds enhanced gastric emptying in rats. Compound 2f not only markedly enhanced gastric emptying but was also a potent agonist at the isolated rat oesophageal tunica muscularis mucosae, a preparation sensitive to 5-HT4 receptor stimulation, and enhanced the twitch response in the LMMP preparation. The latter effect was blocked by a high concentration of tropisetron or by previous desensitization with 5-methoxytryptamine. Compound 2f appears to show a promising pharmacological profile as a potential gastrokinetic agent.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Monge A,Peña MC,Palop JA,Calderó JM,Roca J,García E,Romero G,del Río J,Lasheras Bdoi
10.1021/jm00035a012subject
Has Abstractpub_date
1994-04-29 00:00:00pages
1320-5issue
9eissn
0022-2623issn
1520-4804journal_volume
37pub_type
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