• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.195-206
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• 1995

The study was undertaken to examine the possibility of the involvement of $K^+$ channels in the mechanism of relaxant-action of imipramine on the isolated canine detrusor muscle strips. Canine urinary bladder were isolated, and smooth muscle strips of 15 mm long and 2 mm wide from the mid-portion of anterior wall were made in the Tyrode solution of $0{\sim}4^{\circ}C$. The strips were prepared for isometric myography in Biancani's isolated muscle chamber containing 1 ml of Tyrode solution, which was maintained with pH 7.4 by aeration with $95%\;O_2/5%CO_2\;at\;37^{\circ}C$. RP 52891, a non-specific $K^+$ channel opener, concentration-dependently suppressed the spontaneous phasic contractions of the detrusor strips. Imipramine, a tricyclic antidepressant, also reduced the spontaneous contractions in a concentration-dependent manner. RP 52891 was more potent than imipramine(p<0.05), and Imipramine was more efficient than RP 52891(p<0.05).Procaine, a voltage-dependent $K^+$ channel blocker, glibenclamide, an ATP-dependent $K^+$ channel blocker, and apamin, a calcium-dependent $K^+$ channel blocker antagonized the relaxant effect of RP 52891, but not of imipramine. Imipramine reduced the electric field stimulation (EFS) -induced contractions concentration-dependently. None of the $K^+$ channel blockers employed for this study, procaine, glibenclamide or apamin antagonized the inhibitory action of imipramine on the EFS-induced contraction. These results suggest that in canine detrusor, the $K^+$ channels of the characteristics of voltage-dependent, ATP-dependent and/or calcium-dependent are exist, and the inhibitory action of imipramine on the contractility of the detrusor is independent from the $K^+$ channels.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.81-89
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• 1992

Enuresis is a common voiding disorder among children. There are several therapeutic regimens for the disorder available today; behavioral therapies, psychotherapy, bladder training, sleep interruption, hypnosis and drug therapy. Recently, the efficacy of drug therapy has been acknowledged, particularly of antidepressants. Among the tricyclic antidepressants, imipramine is most frequently employed for the treatment of enuresis. Present study was undertaken to investigate the mechanism of imipramine on the contractility of urinary bladder in relation to the calcium modulation using isolated strips of rat detrusor urinae. 1. The electric fileld stimulation-induced contraction was abolished by imipramine, but partially inhibited by atropine. 2. Imipramine reduced the basal tone and diminished the phasic activity of detrusor muscle concentration-dependently, which was similar to that of diltiazem, a calcium channel blocker. 3. Imipramine suppressed the maximal responses and shifted the concentration-response curves of bethanechol and ATP to right. 4. Imipramine inhibited the calcium-induced recovery of tension in calcium-free physiologic salt solution (PSS) with a mode of action similar to that of diltizaem. 5. A23187, a calcium ionophore recovered the basal tone which had been reduced by imipramine in normal PSS. 6. In calcium-free PSS, A23187 could recover the abolished basal tone with the pretreatment of imipramine, but it exerted a partial recovery with the pretreatment of TMB-8, an inhibitor of intracellular calcium release. Based on these results, it is suggested that the inhibitory action of imipramine on the detrusor muscle exerted in part by blockade of the muscarinic and purinergic receptors, and interference with the influx of extracellular calcium, but not with the release of intracellular stored calcium, is involved in its mechanism of action.