RS 23597-190 hydrochloride

Cell lines

HT29 cells

Preparation Method

HT29 cells were seeded at a density of 10⁴ cells per well in a 96-well plate, with a final volume of 100µL per well. After incubation for 24h at 37°C and 5%CO₂, the medium was replaced with 200µL of fresh medium containing RS 23597-190 hydrochloride at concentrations of 3.125, 6.25, 12.5, 25, 50, and 100µM. Cells cultured in medium alone served as the negative control. After incubation for 48h at 37°C and 5%CO₂, the medium was removed, and 8µL of MTT reagent (diluted in PBS at a concentration of 4mg/mL) was added to 50µL of fresh medium, resulting in a final concentration of 0.55mg/mL. The plate was incubated again at 37°C and 5%CO₂ for 4h, after which the resulting formazan crystals were dissolved in 50µL of dimethyl sulfoxide and measured spectrophotometrically at 570nm.

Reaction Conditions

0, 3.125, 6.25, 12.5, 25, 50, and 100µM；48h

Applications

RS 23597-190 hydrochloride can inhibit cancer cell growth.

Animal models

Adult male Sprague-Dawley rats

Preparation Method

Effects of RS 23597-190 on the gastroprokinetic effects of SC 49518(a benzamide and selective 5-HT₄R agonist).

As RS 23597-190 hydrochloride has an extremely short biological half-life, this drug was infused intravenously into the animals. Animals were anesthetized with ether. The left femoral vein of each rat was catheterized for intravenous drug administration. The animals were allowed to recover from anesthesia and then placed in a restrainer. Each animal was infused, intravenously, with either vehicle (saline, 20μl/min) or RS 23597-190 hydrochloride (0.1mg/kg/min). Thirty rain later, with the infusion still in progress, each animal was treated, intraperitoneally, with the appropriate dose of SC 49518. Thirty minutes later, each animal was dosed, orally, with 3ml of test meal. Forty-five minutes later, the animals were sacrificed and the amount of test meal emptied was determined using the method described above. For the sake of convenience, this experiment was performed over a period of four days.

Dosage form

0.1mg/kg/min for 4 days; i.v.

Applications

In rats, the gastroprokinetic effects of the benzamide and selective 5-HT₄R agonist SC 49518 were significantly antagonized by the selective 5-HT₄R antagonist RS 23597-190 hydrochloride (dosed at 0.1mg/kg/min, i.v.).

References:
[1]Ataee R, Ajdary S, Rezayat M, Shokrgozar MA, Shahriari S, Zarrindast MR. Study of 5HT3 and HT4 receptor expression in HT29 cell line and human colon adenocarcinoma tissues. Arch Iran Med. 2010 Mar;13(2):120-5.
[2]Hegde SS, Wong AG, Perry MR, Ku P, Moy TM, Loeb M, Eglen RM. 5-HT4 receptor mediated stimulation of gastric emptying in rats. Naunyn Schmiedebergs Arch Pharmacol. 1995 Jun;351(6):589-95.