Prostaglandin F2a tris salt
[CAS# 38562-01-5]

Identification

• Classification: Analytical chemistry >> Standard >> Pharmacopoeia standards and magazine standards
• Name: Prostaglandin F2a tris salt
• Synonyms: Prostaglandin F2-alpha tromethamine salt; (5Z,9a,11a,13E,15S)-9,11,15-Trihydroxyprosta-5,13-dienoic acid tris salt
• Molecular Formula: C₂₀H₃₄O₅.C₄H₁₁NO₃
• Molecular Weight: 475.62
• CAS Registry Number: 38562-01-5
• EC Number: 254-002-3
• SMILES: CCCCC[C@@H](/C=C/[C@H]1[C@@H](C[C@@H]([C@@H]1C/C=CCCCC(=O)O)O)O)O.C(C(CO)(CO)N)O

Properties

• Solubility: DMSO: 100 mM, ethanol: 100 mM (Expl.)

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H302-H319-H360
• Safety Statements: P203-P264-P264+P265-P270-P280-P301+P317-P305+P351+P338-P318-P330-P337+P317-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Repr.	1B	H360
Eye irritation	Eye Irrit.	2A	H319
Serious eye damage	Eye Dam.	1	H318

Discovery and Applications

Prostaglandin F_2α tris salt is a water-soluble salt form of prostaglandin F_2α (PGF_2α), developed to improve the stability and solubility of the naturally occurring prostaglandin for pharmaceutical use. PGF_2α is a member of the prostaglandin family, a group of bioactive lipids derived from arachidonic acid via the cyclooxygenase pathway. Naturally occurring PGF_2α plays key roles in reproductive physiology, including the induction of luteolysis, uterine contraction, and cervical ripening, and has been used therapeutically to induce labor or terminate pregnancy, as well as to treat postpartum hemorrhage and glaucoma.

The tris salt of PGF_2α is formed by neutralizing the free carboxylic acid groups with three equivalents of a suitable base, often tromethamine (tris(hydroxymethyl)aminomethane), resulting in a highly water-soluble compound suitable for aqueous formulations. This salt form enhances the compound’s solubility and stability, allowing for consistent dosing in ophthalmic or injectable preparations, and reducing the tendency for rapid degradation that occurs with the free acid in solution. In ophthalmology, PGF_2α tris salt is used topically to reduce intraocular pressure in patients with glaucoma or ocular hypertension by increasing uveoscleral outflow.

The development of PGF_2α tris salt was informed by studies of structure–activity relationships in the prostaglandin F series, which demonstrated that the carboxylate functionality is critical for receptor binding at FP prostanoid receptors. The tris salt form maintains pharmacological activity while enabling formulation in aqueous solutions, which is particularly important for ocular administration where non-irritating, physiologically compatible solutions are required. Clinical studies have confirmed that the tris salt retains the efficacy of PGF_2α in lowering intraocular pressure, with a safety profile comparable to other prostaglandin analogs.

Therapeutically, PGF_2α tris salt is primarily applied in ophthalmology. It is administered topically as eye drops, where it is absorbed through the cornea and converted, if needed, to the active free acid in situ. Its mechanism involves FP receptor agonism in the ciliary muscle, leading to remodeling of the extracellular matrix and increased aqueous humor outflow. Clinical trials have demonstrated significant reductions in intraocular pressure in patients with glaucoma or ocular hypertension with minimal systemic absorption, which minimizes potential cardiovascular or reproductive side effects.

Beyond ophthalmology, PGF_2α tris salt formulations have also been explored in obstetrics for labor induction due to their uterotonic effects, although other prostaglandin derivatives and analogs are often preferred for clinical convenience and stability. The tris salt provides a chemically stable form of PGF_2α suitable for sterile formulations, making it valuable in settings where accurate dosing and solution stability are critical.

References

Woodward DF, Krauss AH, Chen J, Liang Y (2008) Pharmacological characterization of prostaglandin analogs used in glaucoma therapy: prostamide-related activity of bimatoprost. Journal of Ocular Pharmacology and Therapeutics 24 475–482 DOI: 10.1124/jpet.102.047837

Sharif NA, Kelly CR, Crider JY (2002) Agonist activity of prostaglandin analogs at the cloned human ciliary body FP prostaglandin receptor. Journal of Ocular Pharmacology and Therapeutics 18 313–324 DOI: 10.1089/10807680260218489