Acute biphasic dose-response effects of amantadine hydrochloride on bladder storage in conscious rats

Abstract Parkinson’s disease (PD) causes prevalent lower urinary tract (LUT) dysfunction such as overactive bladder and severely impairs patients’ quality of life. Current management of LUT dysfunction in PD remains unsatisfactory. Amantadine hydrochloride, an anti-Parkinson drug, improves PD movement symptoms clinically, yet its urodynamic dose-response is unclear. This study adopted continuous cystometry in normal male Sprague-Dawley rats to explore amantadine’s bladder regulatory effects. Forty rats were assigned to saline control, 0.3, 3, 30, 100 µmol/kg groups. Four core urodynamic indicators—maximum void volume (MV), inter-void interval (IT), maximum detrusor contraction pressure (MP) and post-void residual volume (RV)—were calculated as fold change against individual baseline. 3 µmol/kg amantadine significantly raised MV and prolonged IT, improving bladder storage capacity. Conversely, 100 µmol/kg extreme dose markedly reduced MV and shortened IT. No dose induced statistically significant changes in MP or RV, indicating amantadine solely regulates bladder storage without impairing voiding efficiency. This work first confirms amantadine exerts non-monotonic biphasic modulation on rodent LUT storage function in vivo. Clinicians may optimize oral amantadine dosage to relieve PD storage LUT dysfunction.