Serotonin (5‐HT)2A/2C receptor agonist 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropane hydrochloride improves detrusor sphincter dyssynergia by inhibiting L‐type voltage‐gated calcium channels in spinal cord injured rats

Aims: To explore the role of voltage‐gated calcium channels (VGCC) in 5‐HT2A/2C receptor agonist 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropane hydrochloride's improvement of spinal cord injury (SCI) induced detrusor sphincter dyssynergia and the expressions of the 5‐hydroxy tryptamine (5‐HT) 2A receptors and VGCCs in lumbosacral cord after SCI. Methods: Female Sprague–Dawley rats were randomized into normal control group and SCI group (N = 15 each). Cystometrogram (CMG), simultaneous CMG, and external urethral sphincter electromyography (EUS‐EMG) were conducted in all groups under urethane anesthesia. Drugs were administered intrathecally during CMG and EUS‐EMG. Rats were euthanized and L6‐S1 spinal cord were acquired for immunofluorescence. Results: In SCI rats, intrathecal administration of 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropane hydrochloride or L‐type VGCC blocker, nifedipine, could significantly increase voiding volume, voiding efficiency, and the number of high‐frequency oscillations. They could also prolong EUS bursting activity duration on EUS‐EMG. Moreover, the effect of 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropane hydrochloride can be eliminated with the combined administration of L‐type VGCC agonist, (±)‐Bay K 8644. No significant differences were observed in CMG after intrathecal administration of T‐type VGCC blocker TTA‐P2. Additionally, immunofluorescence of the lumbosacral cord in control and SCI rats showed that the 5‐HT2A receptor and Cav1.2 immunolabeling‐positive neurons in the anterior horn of the lumbosacral cord were increased in SCI rats. Conclusions: Our study demonstrated that 5‐HT2A/2C agonist 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropane hydrochloride may improve SCI‐induced DSD by inhibiting the L‐type voltage‐gated calcium channel in lumbosacral cord motoneurons. [ABSTRACT FROM AUTHOR]