The effect of p.o. administered
JO 1870 [(-)-1-(p-chlorophenyl)-N,N- dimethyl-1-ethyl(4-phenyl)-but-3-en-1-ylamine, hydrochloride] on the urinary bladder cystometrogram has been investigated in the unanesthetized rat. The effects of
JO 1870 have been compared with those of
morphine and reference drugs currently used for the treatment of
urinary incontinence in humans.
JO 1870 (2.5-25 mg/kg) dose-dependently increased the bladder capacity and the threshold pressure responsible for urination. These effects were antagonized by the i.v. administration of
naloxone (0.2 mg/kg). In comparison,
morphine (2.5-25 mg/kg) moderately increased urinary volume and threshold pressure. Different
anticholinergic drugs (
propantheline bromide, 10 mg/kg;
terodiline, 25 mg/kg;
dicyclomine, 25 mg/kg) had no significant effects on either parameter and the
antidepressant clomipramine (25 mg/kg) decreased both. In vitro,
JO 1870 specifically displaced [3H]-[D-Ala2,MePhe4,Gly5-(ol)]
enkephalin from binding sites in guinea pig whole-brain membranes and rat thalamus; the
sodium shift ratio obtained from [3H]
naloxone binding was 16. These results suggest that
JO 1870 has some
opioid agonist activity.
JO 1870 (2.5-300 mg/kg) had few effects on cardiorespiratory, gastrointestinal or nociceptive systems in rats. Together, these results indicate that
JO 1870 is a nonanticholinergic agent that potently increases bladder capacity, likely through an
opioid mechanism, and may have potential use in the treatment of
urinary incontinence.