Anticonvulsant effect of fosphenytoin in amygdala-kindled rats: comparison with phenytoin

Epilepsy Research
W LöscherU Ebert

Abstract

Phenytoin has been reported to exert variable anticonvulsant effects in the kindling model of complex partial seizures. Phenytoin is only water soluble at a pH of more than 10, and it has been suspected that poor absorption of the drug is responsible for its lack of effect in some experiments. Recently, fosphenytoin, a prodrug of phenytoin, has been developed by phosphorylating phenytoin which makes the drug water soluble at physiological pH while it is rapidly transformed to phenytoin after injection. This study examined the anticonvulsant profile and the absorption after intraperitoneal injection of fosphenytoin, compared to its parental drug phenytoin. The pharmacokinetic parameters of phenytoin and fosphenytoin were compared by determining plasma levels of phenytoin after i.p. injection of 50 mg/kg phenytoin or the equivalent dose of 84 mg/kg of fosphenytoin in non-kindled female Wistar rats. After both injections the maximal plasma concentration of phenytoin was about 30 microg/ml. The relative bioavailability of fosphenytoin was 83%. In contrast to phenytoin, failed injections resulting in non-detectable plasma concentration of phenytoin were almost absent after fosphenytoin. In fully kindled female Wistar rats, fosphenyt...Continue Reading

References

Sep 1, 1978·Neurology·R E CranfordB Kostick
Aug 1, 1987·Electroencephalography and Clinical Neurophysiology·J A Mace, W M Burnham
Jan 1, 1989·Epilepsia·I E LeppikP Turlapaty
Jan 1, 1989·Epilepsia·T R BrowneC M McEntegart
Jan 1, 1989·Epilepsia·R D SmithW L Matier
Nov 1, 1989·Annals of Neurology·J O McNamaraC Shin
Jul 1, 1986·Experimental Neurology·W LöscherS J Czuczwar
Jan 1, 1988·Journal of Neural Transmission·M SchmutzV Baltzer
Mar 1, 1972·Electroencephalography and Clinical Neurophysiology·R J Racine
Oct 1, 1967·American Heart Journal·S LouisF McDowell
Jan 1, 1984·Annals of Neurology·J O McNamara
Jan 1, 1980·Electroencephalography and Clinical Neurophysiology·A L Ehle
Jul 1, 1980·Neuropharmacology·T E AlbertsonL G Stark
Nov 1, 1980·Neuropharmacology·D A Callaghan, W S Schwark
Sep 26, 1997·Naunyn-Schmiedeberg's Archives of Pharmacology·U EbertW Löscher
Nov 19, 1997·Progress in Neurobiology·W Löscher

❮ Previous
Next ❯

Citations

Apr 7, 2004·Epilepsy Research·Juan A BarciaM Eugenia Hernández
Apr 20, 2000·Epilepsy Research·W LöscherU Ebert
Apr 11, 2000·Epilepsia·E ReissmüllerW Löscher
Nov 12, 2013·Computers in Biology and Medicine·Arturo SoteloYuliana Martínez
May 14, 2004·The Journal of Pharmacology and Experimental Therapeutics·A J WilliamsJ A Hartings
Jun 3, 2021·Polymers·Natalia Guerrero-AlburquerqueWim J Malfait

❮ Previous
Next ❯

Related Concepts

Related Feeds

Amygdala: Sensory Processes

Amygdalae, nuclei clusters located in the temporal lobe of the brain, play a role in memory, emotional responses, and decision-making. Here is the latest research on sensory processes in the amygdala.

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.