FP receptor

Travoprost is an ester that acts as a pro-drug of a fluoro analogue of prostaglandin PGF200 which is a full agonist of the prostaglandin F (FP) receptor. It is marketed for the topical treatment of intra-ocular hypertension and glaucoma (Fig. 72) [167]. 

Y. Matsumura, N. Mori, T. Nakano, H. Sasakura, T. Matsugi, H. Hara, Y. Morizawa, Synthesis of the highly potent prostanoid FP receptor agonist, AFP-168 A novel 15-deoxy-15,15-difluoroprostaglandin p2 derivative. Tetrahedron Lett. 45 (2004) 1527-1529. 

In the search for a new FP receptor agonist having more potent lOP-reducing activity and weaker side effects, our research group has recently discovered a 15-deoxy-15,15-difluoro-PGF2a derivative, tafluprost (AFP-168), which shows highly potent and selective affinity to the FP receptor [71],... 

Table 5. Affinity of PGF2 derivatives for the human prostanoid FP receptor...

Sharif et al. reported 11-deoxy-16-fluoro-PGF2 , AL-3138 [79], and 11)S-fluoro-15 S-hydroxy-PGF2a analog, AL-8810 [80], as FP receptor antagonists. The synthesis of AL-8810 was shown in Scheme 6 [81]. The fluorination of... 

T. Ota, M. Aihara, S. Narumiya, M. Araie, The effects of prostaglandin analogues on lOP in prostanoid FP-receptor-deficient mice. Invest. Ophthalmol. Vis. Sci. 46 (2005) 4159. 

B.W. Griffin, P. Klimko, J.Y. Crider, N.A. Sharif, AL-8810 A novel prostaglandin F2 alpha analog with selective antagonist effects at the prostaglandin F2 alpha (FP) receptor, J. Phamacol. Exp. Then 290 (1999) 1278. 

Mechanism of Action An ophthalmic agent that is a prostanoid selective FP receptor agonist. Therapeutic Effect Reduces intraocular pressure (lOP) by reducing aqueous humor production. 

The success of latanoprost has stimulated development of similar prostanoids with ocular hypotensive effects, and bimatoprost, travaprost, and unoprostone are now available. These drugs act at the FP receptor and are administered as drops into the conjunctival sac once or twice daily. Adverse effects include irreversible brown pigmentation of the iris and eyelashes, drying of the eyes, and conjunctivitis. 

FP-receptors PGp2 > PGD2 > PGE2 > PGI2 = TBA2. The receptor couples to the IP3/DAG system. Selective agonists include fluprostenol and latanoprost. 

The properties of the prostanoid receptors, such as second messengers in signal transduction pathways, and localization in the eye are summarized in Table 2.1. Prostanoid receptors are widely distributed in the monkey and human eyes [5]. The expression and localization of the FP and EP receptor subtypes in the tissues was studied intensely by in-situ hybridization and immunohistochemistry to gain a better understanding of the ocular effects of the prostanoids and their analogues. This work suggests a wide distribution but differential expression of FP and EP receptor subtypes in human ocular tissues. The highest expression of FP receptor mRNA and protein was found in the corneal epithelium, ciliary... 

Stjernschantz et al. later developed latanoprost [22], which has potent IOP-reducing effects with topical administration once daily in the evening. Compared with a representative (3-blocker, timolol, it demonstrated superior efficacy in clinical studies in reducing IOP by approximately 27-34% from baseline. Latanoprost is the FP receptor agonist most widely used worldwide as an anti-glaucoma drug. 

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