Effects of neurokinin receptor antagonists on L-dopa induced bladder hyperactivity in normal conscious rats

The urodynamic effects of intrathecal neurokinin (NK) receptor blockade on L-dopa-induced bladder hyperactivity were investigated in a rat model.

Continuous cystometry was performed in normal, conscious, female Sprague-Dawley rats.

In rats pretreated with intraperitoneal carbidopa 50 mg./kg., intraperitoneal L-dopa 50 mg./kg. caused bladder hyperactivity that could be attenuated by intrathecal administration of the NK1 receptor selective antagonist SR 140,333 (2 nmol.), whereas the NK2 receptor selective antagonist SR 48,968 (2 nmol.) failed to do so. Combination of SR 140,333 (2 nmol.) and SR 48,968 (2 nmol.), which by itself decreased micturition pressure, practically abolished the L-dopa-induced hyperactivity.

The present results suggest that tachykinins, via stimulation of NK1 (and/or NK2) receptors, are involved in L-dopa-induced bladder hyperactivity, most probably at the spinal level. This implies tachykinin involvement in the supraspinal pathways that control the sacral parasympathetic center innervating the urinary bladder. It also implies that spinal NK receptors are a possible target for drugs aimed for elimination of bladder hyperactivity mediated via these pathways.