title: An automated drug delivery system for focal epilepsy.
abstract: Previous studies have demonstrated the ability to stop seizures in animal models with injection of antiepileptic medication directly onto the seizure focus. The present experiments describe automated detection and focal therapy for seizures in the laboratory setting. Focal seizures were created in Sprague-Dawley rats using bicuculline, a GABA antagonist. Computerized detection of seizures was linked to a programmable infusion pump to deliver either diazepam (DZP) or pH-balanced vehicle (VEH) directly onto the seizure focus. Mean numbers of seizures following initial delivery of drug were 2.9+/-1.45 for the VEH-treated group and 0.2+/-0.42 for the DZP-treated group (P<0.0001, Student's t-test, nonpaired, one-tailed). In another series of experiments, early injection of DZP shortened seizure duration. Three DZP-treated animals died. This model provides proof-in-principle for the development of a clinically applicable treatment for intractable partial epilepsy. Such therapy might avoid some of the problems inherent to systemic administration of antiepileptic drugs.
authors.affiliation: Hawaii Epilepsy Center, Honolulu, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Stein
authors.forename: H G
authors.initials: HG
authors.lastname: Eder
authors.forename: D E
authors.initials: DE
authors.lastname: Blum
authors.forename: A
authors.initials: A
authors.lastname: Drachev
authors.forename: R S
authors.initials: RS
authors.lastname: Fisher
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000627:therapeutic use; D001331:Automation; D001522:Behavior, Animal; D003936:Diagnosis, Computer-Assisted; D003975:Diazepam / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000295:instrumentation; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004867:Equipment Design; D008297:Male; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D014677:Pharmaceutical Vehicles; D003975:Diazepam