8-iso prostaglandin a-1

8-iso Prostaglandin A1 (8-iso PGA1) is an isoprostane and a member in a large family of prostanoids of non-cyclooxygenase origin. It occurs as a common minor impurity in most commercial preparations of PGE1. The biological activity of 8-iso PGA1 has not been studied in depth or reported in the literature.

8-iso PGE2 isopropyl ester is a more lipophilic form of the free acid, 8-iso PGE2. Prostaglandin esters have enhanced lipid solubility compared to their parent compounds. They are generally hydrolyzed to the free acid upon in vivo administration, making the esters useful prodrugs. In general, the C-1 esters of prostaglandins show greatly diminished agonist activity in vitro compared to the parent free acids.

8-iso-15-keto Prostaglandin F2α (8-iso-15-keto PGF2α) is a metabolite of the isoprostane 8-iso PGF2α in rabbits, monkeys, and humans. 8-iso PGF2α is a prostaglandin-like product of non-specific lipid peroxidation. In humans and monkeys, exogenously infused 8-iso PGF2α is converted to metabolites with 2 or 4 carbon atoms removed from the top side chain by β-oxidation, with a similar pattern observed in tritiated 8-iso PGF2α-infused rabbits. Early in the infusion (within 1-2 minutes), 8-iso-15-keto PGF2α is a major component of the metabolite profile, primarily comprising unmetabolized 8-iso PGF2α. 8-iso-15-keto PGF2α is a vasoconstrictor when tested on the rat isolated thoracic aorta, acting via the TP (thromboxane) receptor.

2,3-Dinor-8-iso Prostaglandin F1α (2,3-dinor-8-iso PGF1α), an isoprostane and active metabolite of arachidonic acid deriving its formation from non-enzymatic free radical peroxidation, acts as an active metabolite of the platelet aggregation inhibitor 8-iso PGF2α. This compound exhibits vasoconstrictive properties in isolated porcine retinal and brain microvessels with EC50 values of 12.8 and 18.5 nM, respectively, yet it does not cause contraction in isolated rat aortic rings at a concentration of 31 µM. Further, at a concentration of 1 µM, it raises thromboxane B2 (TXB2) levels in isolated porcine brain slices, an effect reversible by thromboxane A synthase inhibitor CGS 12970, voltage-gated calcium channel inhibitor SKF 96365, or the nicotinic acetylcholine receptor (nAChR) antagonist α-conotoxin.