title: Carbamazepine affects water and electrolyte homoeostasis in rat--similarities and differences to vasopressin antagonism.
abstract: BACKGROUND
  Carbamazepine (CBZ) is a drug widely used in the therapy of epilepsy and mood disorders. One frequently observed side effect is hyponatraemia. The role of vasopressin in hyponatraemic action of CBZ is discussed controversially. In this study, we tested the influence of CBZ on water and salt homoeostasis in rat under different hydration states and under vasopressin 2 receptor (V2R) antagonism by satavaptan to elucidate the renal and vasopressin independent action of CBZ.
  
  
  METHODS
  CBZ-treated rats were investigated on metabolic cages after (i) 6 day with ad libitum fluid intake, (ii) moderate water load and (iii) water restriction. The effect of satavaptan was tested in clearance experiments under continuous saline infusion in anaesthetized rats after CBZ pretreatment.
  
  
  RESULTS
  Compared to controls, CBZ induced a higher urinary flow rate which was most pronounced (20-fold) after water load and significantly elevated (2-fold) after 10-h water restriction. In addition, CBZ consistently increased renal sodium loss but failed to decrease plasma sodium concentration. In the presence of satavaptan, urinary flow and natriuresis were further increased by CBZ, while there was no differential effect on urea excretion and anion gap.
  
  
  CONCLUSIONS
  At the investigated dose (50 mg/kg body weight), CBZ did not induce hyponatraemia or antidiuresis in the rat. However, depending on the hydration state, it induced an increased water and electrolyte loss. Its enhanced influence on urinary flow and natriuresis in the presence of satavaptan suggests additional renal targets for CBZ, independent of vasopressin signalling.
authors.affiliation: Physiologisches Institut der Christian-Albrechts-Universität zu Kiel, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Himmerkus
authors.forename: Birte
authors.initials: B
authors.lastname: Sievers
authors.forename: Markus
authors.initials: M
authors.lastname: Bleich
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D065092:Antidiuretic Hormone Receptor Antagonists; D002220:Carbamazepine / Q000009:adverse effects*; D003681:Dehydration / Q000503:physiopathology; D004231:Diuresis / Q000187:drug effects; D005260:Female; D007010:Hyponatremia / Q000139:chemically induced / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000502:physiology; D013141:Spiro Compounds / Q000494:pharmacology; D014667:Vasopressins / Q000097:blood; D014882:Water-Electrolyte Balance / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000927:Anticonvulsants; D065092:Antidiuretic Hormone Receptor Antagonists; D009025:Morpholines; D017483:Receptors, Vasopressin; D013141:Spiro Compounds; D014667:Vasopressins; D002220:Carbamazepine; C103281:satavaptan