Original Research
Tuesday, October 15, 2024
08:30 AM–10:00 AM
Abstract
Introduction:
We previously reported that one of the oxazolidinone derivatives safely protected most pretreated rats from electrically induced seizures, but for only 30 minutes.
Research Question or Hypothesis:
Do the novel oxazolidinone derivatives PH066, PH162, and PH166 possess potentially favorable physicochemical and pharmacokinetic properties, that will make them exhibit longer anticonvulsant effect in SD rats?
Study Design:
Parallel experimental design
Methods:
Different groups of rats (n=5 each) were pretreated with 100 mg/kg intraperitoneally (IP) of each of the three compounds (synthesized in our laboratory) at 0, 15, 30, 60, 120, 180 minutes prior to induction of seizures with electrical shock. Seizures were videotaped and staged by two trained experimenters based on the classification described previously. Rats experiencing stages 1or 2 seizures were considered protected while rats experiencing stages 4 or 5 are deemed as full seizures. Immediately after evaluating the anticonvulsant effect, rats were euthanized, then blood and brain tissue samples were obtained. The concentrations of the three compounds in rat plasma and brain tissue were measured using LC/MS/MS methods.
Results: The average maximum plasma concentrations were 14.6, 15.0, and 18.1 µg/ml while the average maximum brain tissue concentrations were 2.7, 2.0, and 1.99 µg/gm, and the average brain to plasma distribution ratios were 0.186, 0.156, and 0.131 for PH066, PH162, and PH166, respectively. These relatively good brain distributions for the three compounds resulted in about 80% protection of rats from electrically induced seizures during the first hour, then the brain tissue concentrations declined to reach 0.8, 1.5, and 1.5 µg/gm at the end of three-hour experiment, which was reflected on the 40%, 60%, and 60% rat protection for PH066, PH162, and PH166, respectively.
Conclusion:
The results demonstrate that the three oxazolidinone compounds under investigation display anticonvulsant activity for three hours in most rats. This may be due to the more favorable physicochemical and pharmacokinetic characteristics of these compounds.
Presenting Author
Mohsen Hedaya PharmD, PhDKuwait University
Authors
Naser Altannak PhD
Kuwait University
Samuel Kombian PhD
Kuwait University
Oludotun Phillips PhD
Kuwait University
Mohammad Qaddoumi PhD
Kuwait University
Vidhya Thomas MSc
Kuwait University