Ondansetron

Product Overview

Ondansetron (development code GR-38032) was developed by Glaxo (now GSK) and marketed as Zofran (US)/Zophren; it is the first marketed highly selective 5-HT₃ receptor antagonist and the prototype of its class.

Structural class: A carbazolone—built on a 1,2,3,9-tetrahydro-4H-carbazol-4-one core, methylated at position 9 (indole nitrogen), with a 2-methyl-1H-imidazol-1-yl group attached at position 3 via a methylene linker. This structure mimics the antagonist pharmacophore of serotonin and confers high affinity and selectivity for the 5-HT₃ receptor.

Mechanism of action: Chemotherapeutic agents, radiation, and surgical trauma can damage the gastrointestinal mucosa, prompting enterochromaffin cells to release large amounts of serotonin (5-HT). 5-HT activates 5-HT₃ receptors on vagal afferent terminals in the gastrointestinal tract; the signal is transmitted to the medullary vomiting center and the chemoreceptor trigger zone (CTZ), triggering the emetic reflex. Ondansetron exerts its potent antiemetic effect by blocking 5-HT₃ receptors both peripherally (vagal nerve terminals) and centrally (vomiting center, CTZ), achieving dual blockade at two points of the reflex arc.

Comparative advantages: Compared with traditional antiemetics (e.g., metoclopramide, phenothiazines), ondansetron does not block dopamine D₂ receptors, and therefore does not cause extrapyramidal reactions (no dystonia, akathisia, etc.) and has no sedative effect—two features that make it particularly suitable for outpatient and day-case chemotherapy patients who need to remain alert and mobile.

Salt form note: CAS 99614-02-5 in this entry corresponds to the free base. The form actually used in marketed formulations is ondansetron hydrochloride dihydrate, CAS 99614-01-4, molecular formula C₁₈H₁₉N₃O·HCl·2H₂O, molecular weight 365.85, melting point 178.5–179.5 ℃, pKa 7.4—be sure to distinguish the two forms in procurement and assay conversion.

Chirality note: Position 3 of the molecule is a chiral center; the marketed product is the racemate. The literature gives specific rotation data for the single enantiomers: 3S form [α]D²⁵ −14° (c = 0.19, methanol), 3R form [α]²⁴ +16° (c = 0.34, methanol)—no specific rotation test is set for the racemate.

Technical Specifications

• Standards: CHP/USP/EP (EP has listed “Ondansetron for LC system suitability, EP Standard”, indicating the existence of an EP monograph)

• Specification: 0.99 (purity ≥99.0%, HPLC)

• CAS Numbers:

  • 99614-02-5—ondansetron free base (MDL MFCD00374371; RTECS FE6375500; PubChem; HMDB0005035)
  • 99614-01-4—ondansetron hydrochloride dihydrate (the form used in marketed formulations), C₁₈H₁₉N₃O·HCl·2H₂O, MW 365.85, melting point 178.5–179.5 ℃, pKa 7.4
  • Withdrawn/replaced CAS numbers: 108303-49-7, 116002-70-1, 808754-64-5—if these numbers appear in a data source, they should be updated to 99614-02-5

• Molecular Formula: C₁₈H₁₉N₃O

• Molecular Weight: 293.36 (CAS Common Chemistry 293.36; DrugFuture 293.36; ChemicalBook 293.37; KePu China 293.363; HMDB 293.363); exact mass 293.1528

• Appearance: White to yellow crystals (crystalline solid); the literature records crystallization from methanol

• Purity (HPLC): ≥ 99.0%

• Melting Point: 231–232 ℃ (consistent across multiple sources including CAS Common Chemistry, DrugFuture, ChemicalBook, and KePu China; recommended). Note the distinction: this value corresponds to the free base; the hydrochloride dihydrate (99614-01-4) melts at 178.5–179.5 ℃—the two are different substances and must not be used interchangeably. The above values come from literature/CAplus records, not from a publicly accessible official pharmacopoeial melting point

• Specific Rotation: Not applicable—the marketed product is the racemate (position 3 is a chiral center but is not resolved). Literature values for the single enantiomers: 3S form [α]D²⁵ −14° (c = 0.19, methanol); 3R form [α]D²⁴ +16° (c = 0.34, methanol)

• Chemical Name: 1,2,3,9-Tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one

• Stereochemistry: 1 chiral center (position 3); marketed product is the racemate (±)

• Solubility: Practically insoluble in water; soluble in organic solvents such as methanol, ethanol, DMSO, and dichloromethane (the hydrochloride dihydrate has markedly improved water solubility, which is the main reason it was chosen as the formulation form)

• Acidity Coefficient: pKb 6.50 (ChemicalBook); hydrochloride pKa 7.4

• Calculated Physicochemical Parameters: Density about 1.27–1.275 g/cm³ (20 ℃); boiling point about 546 ℃ (760 mmHg; another calculated value 545.984 ± 30.00 ℃); flash point about 284 ℃; refractive index about 1.691; vapor pressure about 5.6×10⁻¹² (25 ℃); LogP about 3.13 (CAS calculated value); topological polar surface area about 39.82 Ų; H-bond donors 0 / acceptors 3; molar refractivity 86.75

• Marketed Formulation Strengths: Tablets/orally disintegrating tablets 4 mg and 8 mg (calculated as ondansetron); injection 2 mg/mL; oral solution and oral soluble film are also available

• Storage: Store at −20 ℃ (per some sources); seal tightly, protect from light, and store in a dry place; solutions should be prepared freshly before use

Applications

• Prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) (core indication): For nausea and vomiting caused by moderately/highly emetogenic chemotherapy regimens (e.g., cisplatin-containing regimens), including prophylactic and therapeutic use. A foundational agent of standard antiemetic regimens established since the early 1990s

• Radiotherapy-induced nausea and vomiting (RINV): For nausea and vomiting caused by total body irradiation, abdominal radiotherapy, etc.

• Prevention and treatment of postoperative nausea and vomiting (PONV): For the prevention and treatment of nausea and vomiting after surgery under general anesthesia; particularly suitable for outpatient and day-case surgery (owing to its lack of sedation)

• Other exploratory uses (literature reports, not approved indications): Clinical studies have explored its use in bulimia nervosa and early-onset alcohol dependence—these are investigational directions and are not clinical recommendations

• Pharmacology and mechanism research: Used for 5-HT₃ receptor binding and antagonist activity evaluation, 5-HT₃ receptor subtype selectivity studies, emetic reflex pathway research (vagal afferents, CTZ, vomiting center), and gastrointestinal motility and secretion research

• Formulation and manufacturing: Used for formulation development of tablets, orally disintegrating tablets, injections, oral solutions, and oral soluble films; the free base is practically insoluble in water, so formulations mostly use the hydrochloride dihydrate to improve solubility and dissolution; key manufacturing control points include related substances (especially carbazolone core-related impurities and imidazole-substitution by-products), assay, residual solvents, and (where single enantiomers are involved) chiral purity; suitable for analytical method development and validation, stability studies, impurity reference standards, and GMP scale-up and CMO/CDMO contract manufacturing

Safety Notice: This product is a pharmaceutical active ingredient (API) intended solely for compliant industrial, research, and pharmaceutical manufacturing use; it is not intended for end clinical use or self-medication guidance. The finished product is a prescription drug and should be used under physician guidance. Contraindications: contraindicated in patients with hypersensitivity to ondansetron or any component of the formulation. Key warnings: ① QT interval prolongation—ondansetron prolongs the QT interval in a dose-dependent manner, and torsades de pointes (TdP) has been reported; contraindicated in patients with congenital long QT syndrome; use with caution and monitor ECG in patients with electrolyte abnormalities (hypokalemia, hypomagnesemia), congestive heart failure, bradyarrhythmias, or those taking other QT-prolonging drugs/antiarrhythmics; ② Serotonin syndrome—has been reported with concomitant use of other serotonergic drugs (including SSRIs, SNRIs, MAOIs, tramadol, linezolid, methylene blue, etc.), mostly with intravenous administration in combination; monitor for mental status changes, autonomic instability, and neuromuscular hyperactivity; ③ Masking of intestinal obstruction—because it inhibits gastrointestinal motility, use in patients at risk of intestinal obstruction or delayed gastric emptying may mask the symptoms of progressive ileus; monitor patients after abdominal surgery or with chemotherapy-induced reduction of bowel motility; ④ Cross-hypersensitivity—patients hypersensitive to other selective 5-HT₃ receptor antagonists may exhibit cross-hypersensitivity. Most common adverse reactions: headache, constipation, diarrhea, fatigue/somnolence, dizziness; transient elevations of liver function test values (asymptomatic AST/ALT elevations), fever, and injection-site reactions may also occur. Serious adverse reactions: hypersensitivity reactions (urticaria, bronchospasm, laryngospasm, hypotension, anaphylactic shock) and the aforementioned QT prolongation, serotonin syndrome, and masking of intestinal obstruction. Special populations: dose reduction is required in patients with severe hepatic impairment (clearance is markedly reduced); pregnant and lactating women must have risks and benefits weighed by a physician; pediatric dosing must be adjusted by body weight. GHS-related identification for the API: dangerous goods transport code UN 2811 (6.1/PG 3), hazard symbols T, Xi, risk code R25 (toxic if swallowed), WGK Germany 3; wear protective gloves, protective clothing, and respiratory and eye/face protection during handling, and avoid dust inhalation and ingestion.

Product information: please contact us. This information is for reference only.