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The bromo and iodo analogue of compound <jats:bold>13b<\/jats:bold> (2\u2010(1\u2010piperidinyl)ethyl 4\u2010amino\u20105\u2010chloro\u20102\u2010methoxybenzoate) were obtained by halogenation of dechloro\u2010<jats:bold>13b<\/jats:bold> with <jats:italic>N<\/jats:italic>\u2010halogenated succinimides. The series was evaluated in functional <jats:italic>in vitro<\/jats:italic> assays with regard to affinity for serotoninergic 5\u2010HT<jats:sub>4<\/jats:sub>, 5\u2010HT<jats:sub>3<\/jats:sub> and muscarinic M<jats:sub>3<\/jats:sub> receptors. The affinities for 5\u2010HT<jats:sub>4<\/jats:sub> and M<jats:sub>3<\/jats:sub> receptors were below 6.0 (p<jats:italic>K<\/jats:italic><jats:sub>B<\/jats:sub> or pA<jats:sub>2<\/jats:sub>). On 5\u2010HT<jats:sub>4<\/jats:sub> receptors in guinea\u2010pig ileal longitudinal muscle and rat oesophagus, the majority of compounds revealed partial 5\u2010HT<jats:sub>4<\/jats:sub> receptor agonism susceptible to blockade by SDZ 205557, a reference 5\u2010HT<jats:sub>4<\/jats:sub> receptor antagonist (p<jats:italic>K<\/jats:italic><jats:sub>b<\/jats:sub> = 7.25 \u2212 7.73 (guinea\u2010pig ileum) and 7.09 \u2014 7.43 (rat oesophagus)). The relative agonist potency was in the range of 5 \u2013 303 % (5\u2010HT: 100 %). Compound <jats:bold>13b<\/jats:bold> and its bromo analogue <jats:bold>17<\/jats:bold> were the most potent esters of the series. The enantiomers of <jats:bold>13g<\/jats:bold> ((<jats:italic>R<\/jats:italic>)\u2010 and (<jats:italic>S<\/jats:italic>)\u20102\u2010(2\u2010methyl\u20101\u2010piperidinyl)ethyl 4\u2010amino\u20105\u2010chloro\u20102\u2010methoxybenzoate) interacted stereoselectively with 5\u2010HT<jats:sub>4<\/jats:sub> receptors and displayed enantiomeric potency ratios (<jats:italic>R<\/jats:italic>)\/(<jats:italic>S<\/jats:italic>) of 4.3 \u2014 8.7. There was an excellent correlation between (a) antagonist affinity on guinea\u2010pig ileum and rat oesophagus, (b) relative agonist potency on guinea\u2010pig ileum and rat oesophagus, and (c) between antagonist affinity and relative agonist potency within each assay (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup> &gt; 0.91). The new compounds may serve as academic tools in evaluating the functional role of 5\u2010HT<jats:sub>4<\/jats:sub> receptors. The selective partial 5\u2010HT<jats:sub>4<\/jats:sub> receptor agonists presented in this paper may be useful to restore physiological motility and secretion in the gut with reduced or absent propensity to elicit tachycardia and desensitization of the intestinal target receptor.<\/jats:p>","DOI":"10.1002\/ardp.19953280705","type":"journal-article","created":{"date-parts":[[2006,10,17]],"date-time":"2006-10-17T02:37:16Z","timestamp":1161052636000},"page":"585-594","source":"Crossref","is-referenced-by-count":14,"title":["Preparation and <i>In Vitro<\/i> Pharmacology of 5\u2010HT<sub>4<\/sub> Receptor Ligands. 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