Effect of antiepileptic agent, levetiracetam, on urodynamic parameters and neurogenic bladder overactivity in chronically paraplegic rats

Urology. 2009 Apr;73(4):922-7. doi: 10.1016/j.urology.2008.10.056. Epub 2009 Jan 23.

Abstract

Objectives: To investigate the effects of different levetiracetam (LEV) doses on urodynamic parameters in an animal model of neurogenic detrusor overactivity (NDO).

Methods: A total of 54 female rats were studied. Of the 54 rats, 6 served as normal controls, and 48 underwent T10 spinal cord transection (SCT). Of the latter 48 rats, 12 were paraplegic controls, and the remaining 36 rats were divided into 3 equal subgroups that received LEV by way of a subcutaneous osmotic minipump at a dose of 17, 54, and 108 mg/kg daily, respectively. The paraplegic control and treatment groups were further subdivided (n = 6), and cystometry was performed at 3 and 4 weeks after SCT, respectively.

Results: All paraplegic controls developed NDO, with spontaneous contractions. At 3 and 4 weeks after SCT, the mean frequency of the contractions was 1.6 +/- 0.3/min and 1.7 +/- 0.2/min. The contraction amplitude and bladder capacity were not significantly different. After 1 week of LEV treatment, these urodynamic parameters improved significantly in a dose-dependent manner, and the changes were more striking at 2 weeks. At a LEV dosage of 17, 54, and 108 mg/kg, respectively, the NDO frequency increased from 1.7 +/- 0.3 to 0.7 +/- 0.2 contractions/min (P = .01), 0.48 +/- 0.16 contractions/min (P = .009), and 0.5 +/- 0.17 contractions/min (P = .01). The bladder capacity increased from 0.51 +/- 0.1 mL to 1.5 +/- 0.2 mL (P = .0001), 2.5 +/- 1.7 mL (P = .006), and 2.6 +/- 0.3 mL (P = .0003), and the micturition pressure improved from 105.8 +/- 6.9 to 73.8 +/- 6.8 cm H(2)O (P = .01), 58.6 +/- 8.9 cm H(2)O (P = .006), and 49.7 +/- 8.9 cm H(2)O (P = .002).

Conclusions: The results of our study have shown that LEV is an effective treatment of NDO after SCT in rats. It might prove to be a novel, alternative therapeutic approach to NDO. The follow-up of these experimental results with a clinical trial is warranted.

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacology*
  • Chronic Disease
  • Dose-Response Relationship, Drug
  • Female
  • Levetiracetam
  • Paraplegia / complications*
  • Piracetam / administration & dosage
  • Piracetam / analogs & derivatives*
  • Piracetam / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Urinary Bladder, Neurogenic / etiology*
  • Urinary Bladder, Neurogenic / physiopathology*
  • Urinary Bladder, Overactive / etiology*
  • Urinary Bladder, Overactive / physiopathology*
  • Urodynamics / drug effects*

Substances

  • Anticonvulsants
  • Levetiracetam
  • Piracetam