Rivenprost

Rivenprost is a prodrug of the active free acid form, an agonist of the PGE₂ receptor subtype EP₄.^1,2 Rivenprost (tested as the free acid) is selective for the EP₄ receptor over the EP₃, EP₂, and EP₁ receptor subtypes (K_is = 0.7, 56, 620, and >10,000 nM, respectively). It enhances bone morphogenic protein-induced increases in alkaline phosphatase activity, a marker of osteoblastic differentiation, in primary mouse calvarial osteoblasts when used at a concentration of 100 nM.³ Rivenprost decreases LPS-induced increases in plasma TNF-α levels in rats in a dose-dependent manner.¹ It decreases trabecular separation, as well as increases bone volume, in rats when administered at a dose of 10 µg/kg.⁴ Rivenprost (3 and 10 mg/kg) increases proximal tibiae biomechanical strength in ovariectomized rats.⁵

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1. Maruyama, T., Asada, M., Shiraishi, T., et al. Design and synthesis of a highly selective EP₄-receptor agonist. Part 2: 5-Thia and 9ß-HaloPG derivatives with improved stability. Bioorg. Med. Chem. Lett. 11(15), 2033-2035 (2001).

2. Miyamoto, M., Ito, H., Mukai, S., et al. Simultaneous stimulation of EP₂ and EP₄ is essential to the effect of prostaglandin E₂ in chondrocyte differentiation. Osteoarthritis Cartilage 11(9), 644-652 (2003).

3. Nakagawa, K., Imai, Y., Ohta, Y., et al. Prostaglandin E₂ EP₄ agonist (ONO-4819) accelerates BMP-induced osteoblastic differentiation. Bone 41(4), 543-548 (2007).

4. Ito, M., Nakayama, K., Konaka, A., et al. Effects of a prostaglandin EP₄ agonist, ONO-4819, and risedronate on trabecular microstructure and bone strength in mature ovariectomized rats. Bone 39(3), 453-459 (2006).

5. Ninomiya, T., Hosoya, A., Hiraga, T., et al. Prostaglandin E₂ receptor EP₄-selective agonist (ONO-4819) increases bone formation by modulating mesenchymal cell differentiation. Eur. J. Pharmacol. 650(1), 396-402 (2011).