Effects of the selective prostacyclin receptor antagonist RO3244019 on the micturition reflex in rats.

Purpose: We investigated the role of prostacyclin on afferent modulation of the micturition reflex using the novel selective prostacyclin receptor antagonist RO3244019 in rat models of bladder function.

Materials And Methods: The effects of RO3244019 on urodynamic parameters were evaluated in 3 rat models. In the anesthetized isovolumetric bladder contraction and the volume induced micturition reflex (Refill) models the effects of RO3244019 and chronic capsaicin desensitization were compared.

The role of the prostacyclin receptor antagonist RO3244019 in treating neurogenic detrusor overactivity after spinal cord injury in rats.

Objective: To determine the effects of the prostacyclin receptor (IP) antagonist RO3244019 on neurogenic detrusor overactivity (NDO) in spinal cord-injured (SCI) neurogenic bladder of the rat.

Materials And Methods: Female Sprague-Dawley rats with SCI were divided into four treatment groups of eight each: vehicle (200 mm Tris base), indomethacin (3 mg/kg), RO3244019 (at 1 and 5 mg/kg). The conscious rats were assessed by cystometry, by slowly infusing the bladder with physiological normal saline at 0.

RO1138452 and RO3244794: characterization of structurally distinct, potent and selective IP (prostacyclin) receptor antagonists.

Prostacyclin (PGI2) possesses various physiological functions, including modulation of nociception, inflammation and cardiovascular activity. Elucidation of these functions has been hampered by the absence of selective IP receptor antagonists. Two structurally distinct series of IP receptor antagonists have been developed: 4,5-dihydro-1H-imidazol-2-yl)-[4-(4-isopropoxy-benzyl)-phenyl]-amine (RO1138452) and R-3-(4-fluoro-phenyl)-2-[5-(4-fluoro-phenyl)-benzofuran-2-ylmethoxycarbonylamino]-propionic acid (RO3244794).

Discovery and SAR development of 2-(phenylamino) imidazolines as prostacyclin receptor antagonists [corrected].

On the basis of screening hits (1a,b), a series of selective, high affinity prostacyclin receptor antagonists was developed. The optimized lead compound 25d [(4,5-dihydro-1H-imidazol-2-yl)-[4-(4-isopropoxybenzyl)phenyl]amine] had analgesic activity in the rat.