title: Amitriptyline eliminates calculi through urinary tract smooth muscle relaxation.
abstract: BACKGROUND
  We investigated the effects of amitriptyline in the urinary tract smooth muscle and urolithiasis.
  
  
  METHODS
  Cats presenting with obstructive acute renal failure (ARF) received amitriptyline, and renal function and survival rates were analyzed. Isometric contractions and membrane potentials of rat, pig, or human isolated urinary tract smooth muscle were recorded in the presence or absence of amitriptyline.
  
  
  RESULTS
  Twenty cats with obstructive ARF caused by urethral plugs received amitriptyline. In all cases, plugs were completely eliminated, and renal function returned to normal, with a 100% survival rate in the follow-up. Amitriptyline produced potent relaxations in rat urethral strips, accompanied by significant reductions in urethral ring membrane potential. This effect was prevented by pretreatment of urethral rings with 4-aminopyridine (4-AP), a voltage-dependent potassium channel blocker. Amitriptyline abolished in a reversible manner acetylcholine-, bradykinin-, and KCl-induced contractions in rat isolated bladder, and this effect was also prevented by 4-AP. Of interest, spontaneous and KCl-induced contractions of pig and human isolated ureter were also blocked by amitriptyline.
  
  
  CONCLUSIONS
  Our results indicate that amitriptyline is an effective and potent relaxant of urinary tract smooth muscle and this effect is mediated by opening of voltage dependent-potassium channels. We suggest that amitriptyline administration may help to promote elimination of urinary calculi.
authors.affiliation: Nephrology Division, Escola Paulista de Medicina/Universidade Federal de São Paulo, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Achar
authors.forename: Rosi A N
authors.initials: RA
authors.lastname: Achar
authors.forename: Therezinha B
authors.initials: TB
authors.lastname: Paiva
authors.forename: Alexandre H
authors.initials: AH
authors.lastname: Campos
authors.forename: Nestor
authors.initials: N
authors.lastname: Schor
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy; D000639:Amitriptyline / Q000627:therapeutic use*; D000818:Animals; D002415:Cats; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D014513:Ureter / Q000187:drug effects / Q000503:physiopathology; D014521:Urethra / Q000187:drug effects / Q000503:physiopathology; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D014545:Urinary Calculi / Q000188:drug therapy*; D014551:Urinary Tract / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D024642:Potassium Channels, Voltage-Gated; D000639:Amitriptyline