Liposome-entrapped phenytoin locally suppresses amygdaloid epileptogenic focus created by db-cAMP/EDTA in rats.
Status epilepticus was induced in rats by injecting a combination of dibutyryl-cAMP (db-cAMP) and ethylenediaminetetraacetic acid (EDTA) into the amygdala (AM), and the effect of phenytoin (PHT), entrapped in liposomes (PHT-L) and given intravenously at 40 mg/kg, on the spiking activity of the AM epileptogenic focus was examined. Electroencephalograms were recorded from the db-cAMP/EDTA-injected AM and the bilateral sensorimotor cortices. One dose of PHT-L, given 30 min after intra-AM db-cAMP, produced immediate and transient seizure suppression, but did not suppress the sequential spiking activity, which lasted for more than 5 h. In contrast, two doses of PHT-L, given 30 and 60 min after intra-AM db-cAMP/EDTA, produced delayed and local suppression of AM discharges, and immediate and transient seizure suppression was also observed. The AM discharges began to be suppressed about 100 min after the second injection of PHT-L injection, with no overt change occurring in cortical spiking activity. This was followed by total seizure suppression about 170 min after the second PHT-L injection. This effect was not observed after one or two injections of PHT alone. When horseradish peroxidase (HRP), to which the blood-brain barrier is impermeable, was entrapped in liposomes (HRP-L) and given intravenously 30 min after intra-AM db-cAMP/EDTA, an accumulation of HRP was found in the db-cAMP/EDTA-injected AM in 2 of the 5 animals tested. With 2 doses of HRP-L given 30 and 60 min after intra-AM db-cAMP/EDTA, the local augmentation of HRP in the AM was found in all 5 of the 5 animals tested. Our findings suggest that: (1) the AM epileptogenic focus created by db-cAMP/EDTA has a high affinity for liposomes, and this factor participates in the local suppression of AM discharges by PHT-L, and (2) two injections of PHT-L are required for the AM to gather an effective amount of PHT-L.
Mori
N
N
Department of Neuropsychiatry, Fukushima Medical College, Fukushima-shi, Japan.
Kurokouchi
A
A
Osonoe
K
K
Saitoh
H
H
Ariga
K
K
Suzuki
K
K
Iwata
Y
Y
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000494:pharmacology; D003994:Bucladesine / Q000037:antagonists & inhibitors; D003864:Depression, Chemical; D004337:Drug Carriers; D004492:Edetic Acid; D008081:Liposomes; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
D000927:Anticonvulsants; D004337:Drug Carriers; D008081:Liposomes; D010672:Phenytoin; D003994:Bucladesine; D004492:Edetic Acid