Synergistic effects of loxoprofen and glycine on the micturition reflex in consciousrats

Abstract

We examined the inhibitory effects of loxoprofen, a cyclooxygenase inhibitor, and glycine, a majorinhibitory neurotransmitter, on the micturition reflex in conscious rats and hypothesized thatthese drugs would interact synergistically to inhibit micturition. Voiding behaviors were assessedusing a metabolic cage. Oral loxoprofen decreased the urinary frequency, and only a high dose(10 mg/kg) significantly reduced the voided volume. With cystometry, intravenous loxoprofen(0.1–3 mg/kg) and glycine (30 and 100 mg/kg) prolonged the intercontraction intervals (ICI) in adose-dependent manner, but did not change the maximum voiding pressure (MVP) in consciousrats. The combination of loxoprofen (3 mg/kg) and glycine (100 mg/kg) strongly prolonged theICI more than with either drug alone. The lowest dose of loxoprofen (0.1 mg/kg) and glycine(30 mg/kg) did not affect either the ICI or the MVP, but their combination resulted in a significantincrease in the ICI. These results suggest that the combined administration of loxoprofen and glycineproduced a synergistic inhibitory effect on the micturition reflex.