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This study evaluated the interactions between tiagabine (TGB) and three conventional antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), and phenobarbital (PB) in amygdala-kindled rats, a reliable model of complex partial seizures in humans. Isobolographic analysis of interactions revealed that TGB interacted additively with all tested conventional AEDs for the fixed-ratio combinations of 1:3, 1:1, and 3:1. Evaluation of pharmacokinetic interactions between AEDs revealed that the observed additivity was pharmacodynamic in nature. TGB did not affect the plasma and brain concentrations of VPA, CBZ and PB. Similarly, none of the studied conventional AEDs changed the plasma or brain levels of TGB. Also, TGB, VPA, CBZ, and PB administered alone (at their median effective doses) and in combinations at the fixed-ratio of 1:1 did not impair motor performance evaluated in the chimney test. In conclusion, additivity between TGB and conventional AEDs in amygdala-kindled rats and lack of bidirectional pharmacokinetic interactions suggest that TGB appears to be a valuable drug for an add-on therapy of refractory complex partial seizures in humans.

Titel:	Interactions between tiagabine and conventional antiepileptic drugs in the rat model of complex partial seizures.
Autor/in / Beteiligte Person:	Borowicz, KK ; Zadrozniak, M ; Luszczki, JJ ; Czuczwar, SJ
Link:	Zum Volltext
Zeitschrift:	Journal of neural transmission (Vienna, Austria : 1996), Jg. 115 (2008-05-01), Heft 5, S. 661-7
Veröffentlichung:	Wien ; New York : Springer-Verlag, 1996-, 2008
Medientyp:	academicJournal
ISSN:	0300-9564 (print)
DOI:	10.1007/s00702-007-0006-3
Schlagwort:	Amygdala physiopathology Analysis of Variance Animals Anticonvulsants pharmacokinetics Behavior, Animal drug effects Disease Models, Animal Dose-Response Relationship, Drug Drug Interactions Epilepsies, Partial etiology Epilepsies, Partial pathology Male Nipecotic Acids pharmacokinetics Rats Rats, Wistar Severity of Illness Index Tiagabine Anticonvulsants therapeutic use Epilepsies, Partial drug therapy Nipecotic Acids therapeutic use
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [J Neural Transm (Vienna)] 2008 May; Vol. 115 (5), pp. 661-7. <i>Date of Electronic Publication: </i>2008 Jan 11. MeSH Terms: Anticonvulsants / therapeutic use ; Epilepsies, Partial / drug therapy ; Nipecotic Acids / *therapeutic use ; Amygdala / physiopathology ; Analysis of Variance ; Animals ; Anticonvulsants / pharmacokinetics ; Behavior, Animal / drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Interactions ; Epilepsies, Partial / etiology ; Epilepsies, Partial / pathology ; Male ; Nipecotic Acids / pharmacokinetics ; Rats ; Rats, Wistar ; Severity of Illness Index ; Tiagabine References: Neuropsychopharmacology. 2003 Oct;28(10):1817-30. (PMID: 12865900) ; Brain Res Mol Brain Res. 1994 Oct;26(1-2):47-54. (PMID: 7854065) ; Naunyn Schmiedebergs Arch Pharmacol. 2004 Apr;369(4):434-46. (PMID: 14985937) ; Arzneimittelforschung. 1953 Jun;3(6):285-90. (PMID: 13081480) ; Epilepsy Res. 2002 Nov;52(1):15-23. (PMID: 12445956) ; Epilepsy Res. 1997 Jul;28(1):63-72. (PMID: 9255600) ; Seizure. 2004 Dec;13(8):574-81. (PMID: 15519917) ; Seizure. 2004 Oct;13(7):478-80. (PMID: 15324825) ; Eur J Pharmacol. 2005 Jun 15;516(3):212-8. (PMID: 15958264) ; Pharmacol Rev. 1995 Jun;47(2):331-85. (PMID: 7568331) ; Epilepsia. 1997;38 Suppl 1:S9-17. (PMID: 9092952) ; Seizure. 2000 Sep;9(6):431-5. (PMID: 10986002) ; Pharmacol Biochem Behav. 2003 May;75(2):319-27. (PMID: 12873622) ; Life Sci. 1997;61(26):PL 417-25. (PMID: 9416783) ; Pharmacol Rev. 1989 Jun;41(2):93-141. (PMID: 2692037) ; Epilepsy Res. 2000 Oct;41(3):245-51. (PMID: 10962215) ; Lancet. 1998 Jan 17;351(9097):203-7. (PMID: 9449883) ; Naunyn Schmiedebergs Arch Pharmacol. 2005 Jul;372(1):41-54. (PMID: 16133488) ; Eur J Pharmacol. 1990 Apr 25;179(3):463-8. (PMID: 2364995) ; J Pharmacol Exp Ther. 1949 Jun;96(2):99-113. (PMID: 18152921) ; Pharmacol Biochem Behav. 2004 May;78(1):103-10. (PMID: 15159139) ; Epilepsia. 1997 Sep;38(9):966-74. (PMID: 9579934) ; Epilepsia. 2004 May;45(5):424-35. (PMID: 15101823) ; Epilepsia. 1995 Jun;36(6):605-11. (PMID: 7555975) ; Curr Opin Neurol. 1997 Apr;10(2):121-8. (PMID: 9147003) Substance Nomenclature: 0 (Anticonvulsants) ; 0 (Nipecotic Acids) ; Z80I64HMNP (Tiagabine) Entry Date(s): Date Created: 20080115 Date Completed: 20080826 Latest Revision: 20181201 Update Code: 20231215

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Interactions between tiagabine and conventional antiepileptic drugs in the rat model of complex partial seizures.