Intraventricular administration of gabapentin in the rat increases flurothyl seizure threshold.
BACKGROUND
We investigated efficacy of prolonged intraventricular gabapentin (GBP) infusion in the rat flurothyl epilepsy model.


METHODS
Sprague-Dawley rats, under anesthesia, were implanted with bilateral Alzet model 2001 osmotic pumps. The pumps infused GBP 80 microg/microL (3.8 mg/day) or isotonic saline control at 1.0 microL/h into each ventricle for 5 days. After 5 days of GBP infusion, seizures were induced by flurothyl dripped onto filter paper. Time to first myoclonic jerk, first partial seizure and first tonic-clonic seizure was recorded by an observer unaware of the treatment group. Determination of seizures was behavioral.


RESULTS
Data were obtained from 54 rats. First tonic-clonic seizure was at 295.8+/-58.8s (n=28) for control rats, versus 338.0+/-89.9 s (n=26) for rats with GBP in the pump (p=0.049). First myoclonic jerk occurred at 158.7+/-20.8 versus 164.6+/-33.5 s (p=0.44, n.s.). Regression of time to seizure versus weight was not significant. No animal had measurable serum levels (<1 microg/ml) of GBP. The distribution of GBP in brain was not studied, but qualitative observations of methylene blue dye installed in the pumps showed dye in periventricular white matter and also over cortex, especially ipsilaterally.


CONCLUSIONS
GBP instilled into the lateral ventricles by pump for 5 days delays onset of generalized tonic-clonic seizures produced by flurothyl in the rat. Time to first myoclonic or partial seizure was not influenced. Effects were not due to systemic absorption of GBP. This study provides a proof-in-principle for intraventricular therapy with AEDs.
Oommen
Joseph
J
Department of Neurology, University of Texas at Galveston, United States.
Kraus
Alli C
AC
Fisher
Robert S
RS
D000588:Amines / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003292:Convulsants / Q000037:antagonists & inhibitors; D003509:Cyclohexanecarboxylic Acids / Q000097:blood / Q000494:pharmacology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D005481:Flurothyl / Q000037:antagonists & inhibitors; D000077206:Gabapentin; D007276:Injections, Intraventricular; D008751:Methylene Blue; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D013194:Staining and Labeling; D013997:Time Factors; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000097:blood / Q000494:pharmacology*
D000588:Amines; D000927:Anticonvulsants; D003292:Convulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D005481:Flurothyl; D008751:Methylene Blue