PMID- 24905515
OWN - NLM
STAT- MEDLINE
DCOM- 20150209
LR  - 20200106
IS  - 2299-5684 (Electronic)
IS  - 1734-1140 (Linking)
VI  - 66
IP  - 3
DP  - 2014 Jun
TI  - Orphenadrine-induced convulsive status epilepticus in rats responds to the NMDA 
      antagonist dizocilpine.
PG  - 399-403
LID - S1734-1140(14)00095-4 [pii]
LID - 10.1016/j.pharep.2013.12.007 [doi]
AB  - BACKGROUND: Identification of new molecular targets as well as the new models 
      recapitulating different aspects of pathophysiology of status epilepticus (SE) in 
      humans might prove essential for the breakthrough in the efforts against 
      pharmacoresistance in epilepsy. Recently, we described a new model of generalized 
      convulsive SE induced with orphenadrine (ORPH) in rats with unique 
      characteristics [5]. The current study was aimed at assessing the efficacy of a 
      new generation antiepileptic drugs (AEDs) and some of the experimental agents in 
      suppressing ORPH-evoked seizures in rats. METHODS: ORPH was administered 
      intraperitoneally (ip) in the dose of 80 mg/kg in male Wistar rats. The latency 
      to first seizure, the number of seizure episodes and the duration of overt SE, as 
      well as the incidence of deaths was scored with simultaneous 
      electroencephalographic (EEG) recordings. RESULTS: ORPH induced seizures in 100% 
      of animals at a dose of 80 mg/kg, associated with low mortality and good 
      behavioural outcome. Among new generation AEDs: felbamate, levetiracetam, 
      topiramate, lamotrigine and progabide did not affect the seizure incidence. Among 
      the experimental drugs, only dizocilpine, the non-competitive NMDA antagonist, 
      dose-dependently affected the occurrence of the SE (p<0.001). However, CGP-39551 
      competitive NMDA antagonist, the same as scopolamine and mecamylamine (muscarinic 
      and nicotinic receptors antagonists, respectively) showed no effect. CONCLUSIONS: 
      Based on the above findings, one may speculate that NMDA activation is partly 
      involved in the proconvulsant activity of orphenadrine but may not be the primary 
      pathomechanism. ORPH-induced seizures may provide an interesting option for 
      studying novel targets for pharmacological interventions in status epilepticus.
CI  - Copyright (c) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published 
      by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
FAU - Rejdak, Konrad
AU  - Rejdak K
AD  - Department of Neurology, Medical University of Lublin, Lublin, Poland. Electronic 
      address: krejdak@europe.com.
FAU - Nieoczym, Dorota
AU  - Nieoczym D
AD  - Department of Animal Physiology, Institute of Biology and Biochemistry, Maria 
      Curie-Sklodowska University, Lublin, Poland.
FAU - Czuczwar, Miroslaw
AU  - Czuczwar M
AD  - 2(nd) Department of Anesthesiology and Intensive Care, Medical University of 
      Lublin, Lublin, Poland.
FAU - Kis, Jacek
AU  - Kis J
AD  - Department of Human Anatomy, Medical University of Lublin, Lublin, Poland; 
      Department of Urology and Urological Oncology, Medical University of Lublin, 
      Lublin, Poland.
FAU - Wlaz, Piotr
AU  - Wlaz P
AD  - Department of Animal Physiology, Institute of Biology and Biochemistry, Maria 
      Curie-Sklodowska University, Lublin, Poland.
FAU - Turski, Waldemar A
AU  - Turski WA
AD  - Department of Toxicology, Institute of Agricultural Medicine, Lublin, Poland; 
      Department of Experimental and Clinical Pharmacology, Medical University of 
      Lublin, Lublin, Poland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140402
PL  - Switzerland
TA  - Pharmacol Rep
JT  - Pharmacological reports : PR
JID - 101234999
RN  - 0 (Anticonvulsants)
RN  - 127910-32-1 (CGP 39551)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
RN  - AL805O9OG9 (Orphenadrine)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/analogs & derivatives
MH  - Animals
MH  - Anticonvulsants/pharmacology
MH  - Dizocilpine Maleate/*pharmacology
MH  - Electroencephalography/methods
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - N-Methylaspartate/*antagonists & inhibitors/metabolism
MH  - Orphenadrine/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Seizures/drug therapy/metabolism
MH  - Status Epilepticus/*chemically induced/*drug therapy/metabolism
OTO - NOTNLM
OT  - Dizocilpine
OT  - Orphenadrine
OT  - Rats
OT  - Refractory status epilepticus model
EDAT- 2014/06/07 06:00
MHDA- 2015/02/11 06:00
CRDT- 2014/06/07 06:00
PHST- 2013/05/02 00:00 [received]
PHST- 2013/10/30 00:00 [revised]
PHST- 2013/12/03 00:00 [accepted]
PHST- 2014/06/07 06:00 [entrez]
PHST- 2014/06/07 06:00 [pubmed]
PHST- 2015/02/11 06:00 [medline]
AID - S1734-1140(14)00095-4 [pii]
AID - 10.1016/j.pharep.2013.12.007 [doi]
PST - ppublish
SO  - Pharmacol Rep. 2014 Jun;66(3):399-403. doi: 10.1016/j.pharep.2013.12.007. Epub 
      2014 Apr 2.