Ht3 Receptor Family

In contrast to all other known 5-HT receptors, the 5-HT3 receptor is a ligand-gated ion channel [68]. 5-HT3 antagonists are well known in the literature and several are currently on the market for the treatment of chemotherapy-induced emesis and/ or irritable bowel syndrome [69]. The chemistry and pharmacology of selective 5-HT3 agonists is less well understood, although the state of the art in that area has been reviewed recently [70]. Efforts continue to identify structural variations that are tolerated within the basic 5-HT3 antagonist pharmacophore. SAR studies on fused heterocyclic thiophene analogs resulted in the identification of 21, which displayed good potency for rat 5-HT3 receptors (Ki 3.92nM) and excellent selectivity over 5-HT4 [71]. In a series of benzoisoindolones [72], compound 22 displayed good 5-HT3 affinity (Ki 1.2 nM), in vitro antagonist activity (IC50 12 nM) and blocked the Bezold-Jarisch reflex (ID50 2.8 mg/kg i.v.). Compound 22 also prevented scopolamine-induced amnesia in a passive avoidance test at doses of 0.01-1.0 mg/kg i.p. New thienopyrimidines, represented by 23 [73], displayed moderate affinity for 5-HT3 receptors (Ki 33 nM) and > 100-fold selectivity for 5-HT4. Functional studies suggest that 23 may act as a noncompetitive antagonist.


YM-31636 (24) is the most potent 5-HT3 agonist in a series of indenothiazoles [14]. The compound displayed potent affinity for human 5-HT3 receptors (Ki 0.2 nM) and excellent selectivity for a number of biogenic amine receptors, although data for 5-HT4 were not presented. This compound demonstrated agonist activity in isolated guinea pig colon and anticonstipation effects in ferrets at doses of 0.03-3 mg/kg p.o.

Was this article helpful?

0 0
Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook

Post a comment