Oncogenic studies with felbamate (2-phenyl-1,3-propanediol dicarbamate).
نویسندگان
چکیده
Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novel anticonvulsant that is effective against both chemically and electrically induced seizures in laboratory animals. Oncogenic studies were conducted in mice and rats to establish a preclinical safety profile for this drug. There was an increased incidence of hepatic cell adenoma in male and female mice and in female rats. There was an increased incidence of interstitial cell tumors of the testes in the male rat.
منابع مشابه
Acute, subchronic, and chronic toxicity studies with felbamate, 2-phenyl-1,3-propanediol dicarbamate.
Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novel anticonvulsant that is effective against both chemically and electrically induced seizures in laboratory animals. Acute, subchronic, and chronic studies were conducted in mice, rats, and dogs to establish a preclinical safety profile for this drug. Clinical signs following single intraperitoneal doses included hypoactivity, tremors, de...
متن کاملA mechanistic approach to understanding species differences in felbamate bioactivation: relevance to drug-induced idiosyncratic reactions.
In an attempt to understand the species-selective toxicity of felbamate (2-phenyl-1,3-propanediol dicarbamate, FBM), which is thought to result from bioactivation to 2-phenylpropenal, FBM metabolism was evaluated in rats and humans. The formation of 2-phenylpropenal was monitored by the amount of its mercapturates excreted in urine. The data show a relative 5-fold increase in mercapturate excre...
متن کاملFelbamate increases [3H]glycine binding in rat brain and sections of human postmortem brain.
The anticonvulsant compound felbamate (2-phenyl-1,3-propanediol dicarbamate; FBM) appears to inhibit the function of the N-methyl-D-aspartate (NMDA) receptor complex through an interaction with the strychnine-insensitive glycine recognition site. Since we have demonstrated previously that FBM inhibits the binding of [3H]5, 7-dichlorokynurenic acid (DCKA), a competitive antagonist at the glycine...
متن کاملThe chemistry, toxicology, and identification in rat and human urine of 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one: a reactive metabolite in felbamate bioactivation.
4-Hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one has been proposed to be a reactive metabolite of the anti-epileptic drug felbamate [Thompson et al. (1996) Chem. Res. Toxicol. 9, 1225-1229]. 4-Hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one exists in equilibrium with 3-oxo-2-phenylpropyl aminooate, which is known to eliminate to generate 2-phenylpropenal. Thus, this species is postulated to be a latent ...
متن کاملNMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhage in the rat.
Increased levels of glutamate and aspartate have been detected after subarachnoid hemorrhage (SAH) that correlate with neurological status. The NMDA receptor antagonist felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an anti-epileptic drug that elicits neuroprotective effects in different experimental models of hypoxia-ischemia. The aim of this dose-response study was to evaluate the e...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Toxicological sciences : an official journal of the Society of Toxicology
دوره 45 2 شماره
صفحات -
تاریخ انتشار 1998