5-Hydroxytryptamine-3 Receptor Antagonist (5-HT₃ RA). Dolasetron is a first-generation 5-HT₃ receptor antagonist used for the prevention of chemotherapy-induced nausea and vomiting (CINV). [1,2]
Dolasetron Mesylate targets the 5-HT3 (serotonin) receptor. By acting as a selective antagonist, it blocks the binding of serotonin to these receptors, which are found in the central nervous system and the gastrointestinal tract. This action prevents the activation of the vomiting reflex, effectively controlling nausea and vomiting induced by chemotherapy or surgery.

Dolasetron is a first-generation 5-HT₃ receptor antagonist that prevents chemotherapy-induced nausea and vomiting (CINV) by blocking serotonin binding to 5-HT₃ receptors in the gastrointestinal tract and central nervous system. [2]
In vitro, Dolasetron Mesylate is characterized by its high affinity and selectivity for the 5-HT3 receptor. It shows potent antagonist activity in functional assays, blocking serotonin-induced responses in cells expressing the receptor. Its activity is measured by its ability to inhibit the influx of calcium ions or other downstream signaling events triggered by 5-HT3 receptor activation.

Clinical Efficacy – Phase III Trials: In a pooled analysis of four phase III randomized, double-blind trials, dolasetron (100 mg IV) was evaluated in patients receiving moderately emetogenic chemotherapy (MEC). The complete response (CR) rate (no emesis and no rescue antiemetics) for dolasetron in the delayed phase (>24–120 h) was 45% (pooled across older 5-HT₃ RAs), which was significantly lower than the 57% CR rate observed with palonosetron (P < 0.0001). Similarly, the overall CR rate (0–120 h) was 40% for older 5-HT₃ RAs versus 51% for palonosetron (P < 0.0001). [2]
Clinical Efficacy – Retrospective Claims Analysis: In a retrospective database analysis of 26,974 patients receiving single-day emetogenic chemotherapy, dolasetron was among the 5-HT₃ RAs evaluated. The overall delayed CINV rate at cycle 1 was 15.6%, with dolasetron showing a rate of 17.3%. Compared to palonosetron, patients receiving dolasetron had higher odds of delayed CINV in cycle 2 (odds ratio [OR] = 1.65; 95% CI: 1.27–2.15; P = 0.002). This trend continued through subsequent cycles, though not all ORs reached statistical significance. Over 6 cycles of chemotherapy, dolasetron was associated with an additional $148,960 in CINV-related charges compared to palonosetron. [1]
Clinical Safety: The incidence of treatment-related adverse events (AEs) with dolasetron was 27.5% (pooled across older 5-HT₃ RAs), similar to palonosetron 0.25 mg (20.0%) and 0.75 mg (26.5%). The most common treatment-related AEs were constipation (9.2%) and headache (7.4%). [2]
In vivo, Dolasetron Mesylate is an established antiemetic. Clinical studies have demonstrated its efficacy in reducing the incidence and severity of chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). It is available in both oral and intravenous formulations, providing flexibility in clinical use.

The in vitro receptor binding assay for Dolasetron Mesylate involves competitive binding studies. Membranes from cells expressing the 5-HT3 receptor are incubated with a radiolabeled antagonist, such as [3H]-GR65630, in the presence of varying concentrations of the test compound. The amount of radioligand displaced is measured to determine the binding affinity (Ki).

In vitro cell-based functional assays utilize cells that natively express or are engineered to express the 5-HT3 receptor. Cells are loaded with a calcium-sensitive fluorescent dye. Upon stimulation with a 5-HT3 agonist like serotonin, an increase in intracellular calcium is observed. The antagonist's ability to inhibit this calcium flux is measured, and the IC50 is calculated.

We analyzed patient-level data derived from four randomized, double-blind, phase III studies that compared palonosetron at doses of 0.25 mg or 0.75 mg against ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg. The primary endpoints comprised complete response (CR), defined as no emesis and no use of rescue antiemetics, during the acute (0–24 h), delayed (>24–120 h), and overall (0–120 h) phases following chemotherapy. Additional endpoints included complete control (CC), characterized by no emesis, no rescue antiemetics, and no more than mild nausea, the number of emetic episodes, and the severity of nausea.
In vivo animal experiments are not standard for clinical development, as the drug's efficacy in humans is well-established. However, in preclinical studies, the antiemetic effect of Dolasetron Mesylate is often evaluated in ferrets or dogs, which have a vomiting reflex similar to humans. Emesis is induced by a chemotherapeutic agent like cisplatin, and the compound's ability to reduce the number of vomiting episodes is assessed.

Dolasetron Mesylate hydrate is a water-soluble compound. It is administered orally or intravenously, with good bioavailability. It is metabolized in the liver, primarily by CYP2D6, to its active metabolite, hydrodolasetron. The drug and its metabolites are excreted in urine. It is typically stored at room temperature as a solid powder.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Information regarding the use of dolasetron during lactation is limited. Until more data becomes available, caution should be exercised when using dolasetron during lactation. Alternative medications may be considered.
◉ Effects on Breastfed Infants
A double-blind study randomized 160 women undergoing elective cesarean section with spinal anesthesia to two groups. One group received patient-controlled intravenous analgesia (PCA) with sufentanil (standard treatment), while the other group received PCA with dexmedetomidine in addition to standard treatment. Dexmedetomidine was administered at a dose of 5 mcg/kg, followed by a continuous infusion at a rate of 0.5 mcg/kg/hour until the end of the procedure. The latter group received PCA with dexmedetomidine in combination with sufentanil for 2 days post-operatively. Both groups received 25 mg of dolasetron in their PCA solution, and all mothers breastfed. Both groups of newborns had good behavioral and neurological assessments on postpartum days 1 and 2. [1] ◉ Effects on lactation and breast milk A double-blind study randomized 160 women undergoing elective cesarean section under spinal anesthesia to two groups: one group received patient-controlled intravenous analgesia (PCA) with sufentanil (standard treatment), and the other group received PCA with dexmedetomidine in addition to standard treatment. The dose of dexmedetomidine was 5 mcg/kg, followed by a continuous infusion at a rate of 0.5 mcg/kg/hour until the end of the surgery. The latter group received dexmedetomidine in combination with PCA with sufentanil on postoperative day 2. Both groups had 25 mg of dolasetron added to their PCA solution. Patients treated with dexmedetomidine had a shorter time to first lactation (28 hours vs 34 hours), achieved exclusive breastfeeding more quickly (8 days vs 11 days), and had more milk production on the second postpartum day. [1]
Toxicological data indicate that Dolasetron is generally well-tolerated. Common adverse effects include headache, dizziness, and constipation. It can cause a dose-dependent prolongation of the QT interval, which is a consideration for patients with cardiac conditions. It is contraindicated in patients with known hypersensitivity to the drug.

[1].Faria C, et al. Outcomes Associated with 5-HT3-RA Therapy Selection in Patients with Chemotherapy-Induced Nausea and Vomiting: A Retrospective Claims Analysis. Am Health Drug Benefits. 2014 Jan;7(1):50-8.

[2].Schwartzberg L, et al. Pooled analysis of phase III clinical studies of palonosetron versus ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV). Support Care Cancer. 2014 Feb;22(2):469-77.

[3]. Long-term Use of Ondansetron, Dolasetron and Granisetron for the Prevention of Nausea and Vomiting: A Review of the Clinical Effectiveness and Safety [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2014 Apr 23. Available from http://www.ncbi.nlm.nih.gov/books/NBK269203/ PubMed PMID: 25610941.

Dolasetron mesylate is an indole derivative with antiemetic activity. As a selective serotonin receptor antagonist, dolasetron mesylate competitively blocks the action of serotonin on 5-HT3 receptors, thereby inhibiting nausea and vomiting induced by chemotherapy and radiotherapy. (NCI04)
See also: Dolasetron mesylate (note moved to).
Dolasetron Mesylate is an FDA-approved antiemetic drug. It is used to prevent nausea and vomiting in patients undergoing chemotherapy and for the prevention of postoperative nausea and vomiting. While it has been approved, its use has been somewhat supplanted by newer 5-HT3 antagonists like palonosetron, which have a longer half-life.

C20H26N2O7S

438.4946

438.146

C, 54.78; H, 5.98; N, 6.39; O, 25.54; S, 7.31

878143-33-0

Dolasetron;115956-12-2;Dolasetron Mesylate;115956-13-3

6918119

White to off-white solid powder

178 °C

2.634

3

8

3

30

627

2

CS(=O)(=O)O.C1[C@@H]2CC(C[C@H]3N2CC(=O)C1C3)OC(=O)C4=CNC5=CC=CC=C54.O

QTFFGPOXNNGTGZ-RCSCTSIBSA-N

InChI=1S/C19H20N2O3.CH4O3S.H2O/c22-18-10-21-12-5-11(18)6-13(21)8-14(7-12)24-19(23)16-9-20-17-4-2-1-3-15(16)17;1-5(2,3)4;/h1-4,9,11-14,20H,5-8,10H2;1H3,(H,2,3,4);1H2/t11?,12-,13+,14?;;

methanesulfonic acid;[(3S,7R)-10-oxo-8-azatricyclo[5.3.1.03,8]undecan-5-yl] 1H-indole-3-carboxylate;hydrate

878143-33-0; MDL-73147EF hydrate; Dolasetron mesylate hydrate; DOLASETRON MESYLATE; MDL73147EF hydrate; Dalasetron (Mesylate hydrate); DOLASETRON MESYLATE MONOHYDRATE;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~570.14 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)