Animal models of drug‐resistant epilepsy*

Epileptic Disorders - Tập 14 Số 3 - Trang 226-234 - 2012
Heidrun Potschka1
1Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig–Maximilians-University Munich, Germany

Tóm tắt

ABSTRACT

Several animal models are discussed in order to outline features of difficult‐to‐treat or drug‐resistant epilepsy. These models can be categorised as those which show a poor response to different antiepileptic drugs and those in which subgroups of drug‐resistant animals are selected, based on interindividual differences. Non‐responders to antiepileptic drugs have been described in the amygdala kindling model, as well as the chronic phase of post‐status epilepticus models. Epileptic dogs which do not respond to standard antiepileptic drugs may serve as a translational model to provide a more clinical environment for drug testing. Drug resistance or a poor response to several antiepileptic drugs has been reported for the 6‐Hz model, lamotrigine‐pretreated kindled rats, pentylentetrazole‐induced seizures in rats pre‐exposed to pilocarpine, as well as following intrauterine exposure of rats to methylazoxymethanol. Using models to select non‐responders is highly time‐consuming and elaborate, limiting their use in routine drug‐screening procedures. Current efforts to identify biomarkers of drug resistance may simplify the selection process, e.g. replacing several weeks of seizure monitoring by a single imaging scan. Moreover, further elucidation of mechanisms of resistance may help to design a series of ex vivo or in vitro screening procedures in order to evaluate whether a test compound is affected.

Từ khóa


Tài liệu tham khảo

10.1016/S0920-1211(01)00302-3

10.1111/j.1528-1167.2007.00980.x

10.1016/j.nbd.2008.01.005

10.1111/j.1528-1167.2008.01797.x

10.1111/j.0013-9580.2004.16904.x

10.1016/j.nbd.2006.06.014

10.1111/j.1528-1167.2010.02671.x

10.2460/javma.235.12.1442

10.1016/j.eplepsyres.2005.08.009

10.1016/S0028-3908(00)00039-3

10.1111/j.1528-1167.2008.01659.x

10.1002/(SICI)1097-4547(19980215)51:4<473::AID-JNR7>3.0.CO;2-9

10.1046/j.1528-1157.2002.18101.x

10.1111/j.1528-1167.2010.02886.x

10.1016/S0028-3908(01)00148-4

10.1016/S0301-0082(97)00035-X

10.1016/S0920-1211(02)00073-6

10.1016/j.seizure.2011.01.003

Loscher W, 1991, Kindling as a model of drug‐resistant partial epilepsy: selection of phenytoin‐resistant and nonresistant rats, J Pharmacol Exp Ther, 258, 483

10.1111/j.1528-1167.2009.02183.x

10.1016/0014-4886(86)90160-3

10.1016/0920-1211(93)90058-F

10.1016/S0920-1211(00)00108-X

10.1111/j.0013-9580.2004.21204.x

10.1016/j.eplepsyres.2008.10.010

10.1136/vr.159.26.881

10.1111/j.1499-1654.2000.001514.x

10.1097/01.wnr.0000134840.10390.a4

10.1111/j.1528-1157.2000.tb00176.x

10.1111/j.1535-7511.2008.00272.x

10.1016/0028-3908(90)90159-O

10.1111/j.1535-7511.2008.01289.x

10.1111/j.1365-2885.1985.tb00934.x

10.1016/j.eplepsyres.2004.08.003

10.1016/j.neuropharm.2005.01.013

10.1016/S0920-1211(02)00051-7

Srivastava AK, 2005, Retigabine decreases behavioral and electrographic seizures in the lamotrigine. Resistant amygdale kindled rat model of pharmacoresistant epilepsy, Epilepsia, 46, 217

Srivastava AK, 2006, Felbamate is effective against behavioural and the electrographic seizures in the lamotrigine‐resistant amygdale kindled rat model of refractory epilepsy, Epilepsia, 47, 321

Srivastava AK, 2004, Carbamazepine, but not valproate, displays pharmacoresistance in lamotrigine‐resistant amygdala‐kindled rats, Epilepsia, 45, 12

Srivastava AK, 2007, Levetiracetam decreases behavioral and electrographic seizures in the lamotrigine‐resistant amygdale kindled rat model of pharma‐coresistant epilepsy, Epilepsia, 48, 364

10.1212/WNL.1.11-12.444

10.1093/brain/awh437

10.1016/j.nbd.2005.09.006

10.1016/j.tvjl.2007.03.002

10.1111/j.1748-5827.2006.00290.x

Thông tin
Thông tin xuất bản

Epileptic Disorders

Tập 14 Số 3

226-234

Thông tin tác giả