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Proconvulsant effects of
high doses of venlafaxine in pentylenetetrazole-convulsive
rats.
Santos JG Jr, Do Monte FH, Russi M, Agustine
PE, Lanziotti VM.
Laboratorio de Neurofisiologia,
Departamento de Psicobiologia, Escola Paulista de Medicina, Universidade
Federal de Sao Paulo, Sao Paulo, SP, Brasil.
guistos@mailcity.com
Venlafaxine, an atypical antidepressant
drug, has been used to treat several neurological disorders, presenting
excellent efficacy and tolerability. Clinical seizures after venlafaxine
treatment have occasionally been reported when the drug was used at very
high doses or in combination with other medications. The aim of the
present study was to investigate the convulsant effects of venlafaxine
in rats under controlled laboratory conditions. Adult male Wistar rats
(8 per group) receiving venlafaxine or saline at the doses of 25-150
mg/kg were subjected 30 min later to injections of pentylenetetrazole at
the dose of 60 mg/kg. The animals receiving 75, 100 and 150 mg/kg
venlafaxine presented increased severity of convulsion when compared to
controls (P = 0.02, P = 0.04, and P = 0.0004, respectively). Indeed, an
increased percentage of death was observed in these groups (50, 38, and
88%, respectively) when compared to the percentage of death in the
controls (0%). The group receiving 150 mg/kg showed an reduction in
death latency (999 +/- 146 s) compared to controls (1800 +/- 0 s;
cut-off time). Indeed, in this group, all animals developed seizures
prior to pentylenetetrazole administration. Surprisingly, the groups
receiving venlafaxine at the doses of 25 and 50 mg/kg showed a tendency
towards an increase in the latency to the first convulsion. These
findings suggest that venlafaxine at doses of 25 and 50 mg/kg has some
tendency to an anticonvulsant effect in the rat, whereas doses of 75,
100 and 150 mg/kg presented clear proconvulsant effects in rats
submitted to the pentylenetetrazole injection. These findings are the
first report in the literature concerning the role of venlafaxine in
seizure genesis in the rat under controlled conditions.
PMID:
11960197 [PubMed - indexed for MEDLINE]
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