Tegaserod (maleate)

Tegaserod maleate (SDZ-HTF-919) is an orally active serotonin receptor 4 (HTR4; 5-HT₄R) agonist and a 5-HT_2B receptor antagonist. Tegaserod maleate has pK_is of 7.5, 8.4 and 7.0 for human recombinant 5-HT_2A, 5-HT_2B and 5-HT_2C receptors, respectively. Tegaserod maleate causes tumor cell apoptosis, blunts PI3K/Akt/mTOR signaling and decreases S6 phosphorylation. Tegaserod maleate has anti-tumor activity and has the potential for irritable bowel syndrome (IBS) research^[1][2][3]. In Vitro: Tegaserod maleate (SDZ-HTF-919; 3-5 μM; 24-72 h) causes a significant time and dose-dependent increase in apoptosis^[1].
Tegaserod maleate (3-5 μM; 8-18 h) decreases phosphorylation of the kinase directly upstream of S6, p70 S6 at Thr⁴²¹/Ser^424[1].
Tegaserod maleate (0.1-3 μM; 24h) inhibits 5-HT-mediated contraction of the rat isolated stomach fundus potently (pA₂=8.3), consistent with 5-HT_2B receptor antagonist activity^[3].
In Vivo: Tegaserod maleate (SDZ-HTF-919; 5 mg/kg/day; ip; for five consecutive days) delays tumor growth, reduces metastases, increases survival and suppresses p-S6 in vivo^[1].
Tegaserod maleate (0.1-2.0 mg/kg; IP 15 min prior to gastric loading) significantly accelerates the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80% with 0.1mg/kg^[2].