Elzayat Ehab ¹, Campeau Lysanne ¹, Karsenty Gilles ¹, Blok Bertil ¹, Padjen L. Ante ², and Corcos Jacques ¹

Department of Urology¹and Pharmacology& Therapeutics², McGill University, Montreal, Quebec, Canada

Introduction and Objective: Levetiracetam (LEV) is the racmically pure S-enantiomer of a alpha-ethyl-2-oxo-1-pyrolidineacetatemid, a novel and potent antiepileptic drug. We studied the effect of different doses of LEV on urodynamic parameters of an animal model of overactive bladder (OAB).

Methods: 54 rats were used in this study. 6 rats were normal control, 48 rats underwent a T10 spinal cord transaction (ST). 12 of them served as paraplegic controls, remaining 36 rats were divided into 3 equal groups and received LEV at a dose of 17 mg/kg, 54mg/kg, and 108 mg/kg daily, respectively. The drug was delivered via an osmotic minipump inserted subcutaneously in the back of the animals 2 weeks after ST. Each ‘‘paraplegic control’’ and treatment group was further divided into two sub-groups (n = 6), and filling Cystometry (CMG) was done at 3 and 4 weeks after ST, respectively.

Results Obtained: All ‘‘paraplegic control’’ rats developed neurogenic detrusor overactivity (NDO). At 3 and 4 week after ST respectively, the mean frequency of contractions was 1.6±0.3 and 1.7±0.2 / min, contraction amplitude was 29.7±1.4 and 31.6±2.4 cmH₂O and bladder capacity was 1.1±0.2 and 0.5±0.1 ml. Bladder capacity was 0.62±0.1 ml in the normal control group. After 1 week of treatment urodynamic parameters improved significantly* in a dose-dependent manner, however, improvements were more obvious at 2 weeks: Respectively for LEV dosages of 17, 54, and 108 mg/kg, the frequency of NDO went from1.7±0.3 to 0.7±0.2*, 0.48±0.16*, and 0.5±0.17* contractions /min, the amplitude of NDO went from 31.7±2. cmH₂O to 28.7±1.6, 32.3±3, and 25.3±1.9* cmH₂O, bladder capacity increased from 0.51±0.1 ml to1.5±0.2*, 2.5±1.7*, and 2.6±0.3* ml, and the micturition pressure improved from 105.8±6.9 cmH₂O to 73.8±6.8*, 58.6±8.9*, and 49.7±8.9* cmH₂O.

Conclusions: Levetiracetam is effective in treatment of NDO after ST in rats. Knowing its excellent safety profile in humans, it may provide a novel alternative treatment of OAB. Follow up of these experimental results with clinical trial remains to be done.

* Asterisk indicates statistical significance (p < 0.05).

Source of Funding: USB pharma

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