5-HT4 receptor partial agonist

Pharmacoiogy Tegaserod, a 5-HT4 receptor partial agonist, triggers the release of... 

Muller-Lissner SA, EumagalU I, BardUan KD, et al. Tegaserod, a 5-HT4 receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. AUment Pharmacol Ther 2001 15 1655-1666. 

Tegaserod maleate (Zelnorm) is a partial serotonin (5-HT4) receptor agonist that causes an increase in peristaltic activity and intestinal secretion and moderation of visceral sensitivity. It increases the frequency of bowel movements and reduces abdominal discomfort, bloating, and straining. It is indicated for the treatment of patients younger than 65 years of age who experience chronic idiopathic constipation. The most common adverse effects include headache, abdominal pain, diarrhea, and nausea. 

Lamirault L, Simon H. Enhancement of place and object recognition memory in young adult and old rats by RS 67333, a partial agonist of 5-HT4 receptors. Neuropharmacology 2001 41 844-853. 

Possible functions of the 5-HT4 receptor have been recently reviewed [47,48,49]. In the CNS, 5-HT4 activation increases cAMP in the hippocampus [50]. This observation has led to behavioral studies using cognition models. 5-HT4 receptor activation induces relaxation of the esophagus [51,52] and increases cAMP accumulation in this tissue [53]. These data indicate a possible role for the 5-HT4 receptor in GERD. A selective 5-HT4 partial agonist, cisapride, has been used clinically for gastroprokinesis for many years prior to the elucidation of its molecular site of action. Functional 5-HT4 receptors have also been demonstrated in the guinea pig ileum [54] and in the cardiac atrium, in which increases in cAMP accumulation can also be detected [55]. Such functions indicate possible roles of the 5-HT4 receptor in irritable bowel syndrome and in arrhythmia. 

A subclass of serotonin receptors dubbed 5-HT4 are involved in regulation of intestinal motility. The partial agonist tegaserod (22) has proven useful in treating conditions characterized by decreased motility, such as irritable bowel syndrome. The drug is interestingly prescribed specifically for use in women, since results from clinical trials indicated poor response in men. Alkylation of thiosemicarbazone (18) with methyl iodide proceeds on sulfur to the thioether (19). Treatment of intermediate 19 with pentyl-1-amine leads to addition of the amine to the thioether function followed by... 

By 1988, it was known that the 5-HT-induced tachycardia in pig was neither mimicked nor antagonized by a variety of 5-HTi 2,3-R ligands, and was therefore necessarily mediated by a new subtype of 5-HT-R [89]. A similar observation was made by Kaumann et al. in human atrium, in which a non-5-HTi 2,3-R increased contractile force via an increase in c-AMP and PKA activity [24]. Since this receptor was blocked by mM concentrations of tropisetron, this suggested that 5-HT4-R subtype was involved. Later, it was shown that both right and left hxunan atria express 5-HT4-RS where benzamides are partial agonists [32, 90]. The... 

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