Effects of some antidepressants on the volume-induced reflex contractions of the rat urinary bladder: lack of correlation with muscarinic receptors affinity.
It has been suggested that tricyclic antidepressants such as imipramine, might exert their anti-enuretic action by a blockade of muscarinic receptors in the detrusor muscle of the urinary bladder. We have therefore investigated the effects of two tricyclic (imipramine and nortriptyline) and three atypical (citalopram, amineptine and mianserin) antidepressants on the micturition reflex and muscarinic receptors in rats. The micturition reflex pathway was monitored indirectly by recording the rhythmic intravesical pressure waves which occurred when the bladder was distended and maintained under constant saline-volume. The activity of the antidepressants was correlated to their potencies as antagonists of [3H]QNB binding to rat brain (mainly M1 receptors) and bladder (mainly M2 receptors) membranes, as well as antagonists of carbachol-induced contractions of rat bladder strips. Only imipramine and citalopram dose dependently inhibited the voiding contractions, whereas nortriptyline, imipramine and mianserin (in order of potency) were active both in binding studies and as competitive antagonists of carbachol-induced bladder contractions, but were inactive in inhibiting the micturition reflex. The present data seem to suggest that affinities for muscarinic receptors are unrelated to the inhibition of micturition reflex.
Pietra
C
C
Pharmacology Department, RECORDATI S.p.A., Milan, Italy.
Poggesi
E
E
Angelico
P
P
Guarneri
L
L
Testa
R
R
D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D015283:Citalopram / Q000494:pharmacology; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008803:Mianserin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009661:Nortriptyline / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects
D000928:Antidepressive Agents; D003986:Dibenzocycloheptenes; D011976:Receptors, Muscarinic; D015283:Citalopram; D008803:Mianserin; C011597:amineptin; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D009661:Nortriptyline; D007099:Imipramine