A novel alternative in the treatment of detrusor overactivity? In vivo activity of O-1602, the newly synthesized agonist of GPR55 and GPR18 cannabinoid receptors

Abstract

The aim of the research was to assess the impact of O-1602—novel GPR55 and GPR18 agonist—in the rat model of detrusor overactivity (DO). Additionally, its effect on the level of specific biomarkers was examined. To stimulate DO, 0.75% retinyl acetate (RA) was administered to female rats’ bladders. O-1602, at a single dose of 0.25 mg/kg, was injected intra-arterially during conscious cystometry. Furthermore, heart rate, blood pressure, and urine production were monitored for 24 h, and the impact of O-1602 on the levels of specific biomarkers was evaluated. An exposure of the urothelium to RA changed cystometric parameters and enhanced the biomarker levels. O-1602 did not affect any of the examined cystometric parameters or levels of biomarkers in control rats. However, the O-1602 injection into animals with RA-induced DO ameliorated the symptoms of DO and caused a reversal in the described changes in the concentration of CGRP, OCT3, BDNF, and NGF to the levels observed in the control, while the values of ERK1/2 and VAChT were significantly lowered compared with the RA-induced DO group, but were still statistically higher than in the control. O-1602 can improve DO, and may serve as a promising novel substance for the pharmacotherapy of bladder diseases.