Evaluation of the potentiating effects of antidepressants on the contractile response to noradrenaline in guinea pig urethra smooth muscles.

Abstract

We investigated the potential augmenting effects of 19 clinically available antidepressants on noradrenaline (NA)-induced contractions in guinea pig urethra smooth muscle (USM). Concentration-response curves for NA-induced contractions in guinea pig USM strips were obtained in the absence or presence of selected antidepressants. Desipramine, an active metabolite of imipramine, produced a contraction and potentiated NA-induced contraction at the distal urethra without affecting the proximal urethra. Further, nortriptyline and amoxapine, tricyclic antidepressants, produced a contraction and potentiated NA-induced contraction at the distal urethra. NA-induced contraction was unaffected or reduced by imipramine, clomipramine, trimipramine, and amitriptyline at the proximal and distal urethra. Maprotiline, a tetracyclic antidepressant, potentiated NA-induced contraction at the distal urethra. NA-induced contraction was unaffected by mianserin at the proximal and distal urethra. Paroxetine, a selective serotonin reuptake inhibitor (SSRI), potentiated NA-induced contraction at the distal urethra, while NA-induced contraction was unaffected by fluvoxamine, sertraline, and escitalopram at the proximal and distal urethra. Milnacipran, a serotonin-noradrenaline reuptake inhibitor (SNRI), potentiated NA-induced contraction at the proximal and distal urethra, whereas duloxetine potentiated it at the distal urethra. Mirtazapine slightly inhibited NA-induced contraction at the distal urethra. Aripiprazole and sulpiride did not affect NA-induced contractions at the proximal nor distal urethra. Trazodone inhibited NA-induced contraction at both urethras. Desipramine, nortriptyline, amoxapine, maprotiline, paroxetine, milnacipran, and duloxetine likely induce urinary disturbance by increasing urethral resistance and augmenting NA-induced contraction, which should be carefully considered when delivering guidance for drug administration to patients.