Proconvulsant effects of high doses of venlafaxine in pentylenetetrazole-convulsive rats

Abstract

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. Correspondence

Raster plots machine learning to predict the seizure liability of drugs and to identify drugs

“…However, in recent years, there have also been reports on evaluating seizure-causing compounds using iPS neurons 23 . The results of previous research on in vitro assays 18 , 23 , 35 , 37 – 42 , the concentrations in the present study at which significant differences were observed using conventional burst analysis, the concentrations at which the AI identified seizure liability, and the concentrations at which the AI identified drugs are all summarized in Table 5 . Table 5 shows the concentrations and analysis parameters that were significantly different from those of the vehicle studied in a previous research 18 , 23 , 35 , 37 – 42 and the present study using the conventional analysis method.…”

Venlafaxine Attenuated the Cognitive and Memory Deficit in Mice Exposed to Isoflurane Alone

“…The dose of VLX used in the present study was based on the previous reports. One report claimed that higher doses (75, 100, and 150 mg/kg) of venlafaxine could lower the threshold of convulsion in animals and suggested the use of 25 and 50 mg/kg for animal study (32). Another study found that venlafaxine exerted stimulant effect on mouse activity in a locomotor test from the dose of 16 mg/kg (33).…”

Dual effects of anandamide in the antiepileptic activity of diazepam in pentylenetetrazole-induced seizures in mice

“…Trained observers, blinded to the treatments scored the observation of test sessions. The method used was as earlier reported (Santos et al , 2002; Manna and Umathe, 2012).…”