Influence of aminophylline on the anticonvulsive action of gabapentin in the mouse maximal electroshock seizure threshold model.
Accumulating evidence indicates that aminophylline [theophylline(2) x ethylenediamine] markedly attenuates the anticonvulsant action of conventional antiepileptic drugs in experimental animal models of epilepsy and evokes severe seizure activity in patients treated with this methylxanthine. The objective of this study was to determine the influence of acute (single) and chronic (twice daily for 14 consecutive days) treatments with aminophylline on the anticonvulsant potential of gabapentin (a second-generation antiepileptic drug) in the mouse maximal electroshock seizure threshold model. Additionally, the effects of acute and chronic administration of aminophylline on the adverse effect potential of gabapentin in terms of motor coordination impairment were assessed in the chimney test. To evaluate pharmacokinetic characteristics of interaction between drugs, total brain concentrations of gabapentin and theophylline were estimated with high-pressure liquid chromatography and fluorescence polarization immunoassay, respectively. Results indicated that gabapentin (at doses of 75 and 100 mg/kg, i.p.) increased the threshold for electroconvulsions in mice. Aminophylline in non-convulsive doses of 50 and 100 mg/kg (i.p.), both in acute and chronic experiments, did not attenuate the anticonvulsant potential of gabapentin in the maximal electroshock seizure threshold test in mice. Similarly, aminophylline at a dose of 100 mg/kg had no impact on the adverse effect potential of gabapentin in the chimney test. Pharmacokinetic evaluation of total brain concentrations of gabapentin and theophylline revealed no significant changes in total brain concentrations of the drugs after both, acute and chronic applications of aminophylline in combination with gabapentin. The data show that aminophylline did not alter the ability of gabapentin to protect mice against seizures induced by electroconvulsive shock. The observed interaction between gabapentin and aminophylline in both acute and chronic experiments was pharmacodynamic in nature.
Luszczki
J J
JJ
Department of Pathophysiology, Medical University of Lublin, Lublin, Poland. jluszczki@yahoo.com
Jankiewicz
K
K
Jankiewicz
M
M
Czuczwar
S J
SJ
D000588:Amines / Q000032:analysis / Q000494:pharmacology*; D000628:Aminophylline / Q000032:analysis / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000032:analysis / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry; D001993:Bronchodilator Agents / Q000032:analysis / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003509:Cyclohexanecarboxylic Acids / Q000032:analysis / Q000494:pharmacology*; D004347:Drug Interactions; D004597:Electroshock; D000077206:Gabapentin; D007118:Immunoassay; D008297:Male; D051379:Mice; D011597:Psychomotor Performance / Q000187:drug effects; D012640:Seizures / Q000517:prevention & control*; D013995:Time; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000494:pharmacology*
D000588:Amines; D000927:Anticonvulsants; D001993:Bronchodilator Agents; D003509:Cyclohexanecarboxylic Acids; D000628:Aminophylline; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
Neuropsychopharmacology. 2003 Oct;28(10):1817-30
12865900
J Neural Transm (Vienna). 2006 Sep;113(9):1157-68
16465466
Brain Res. 1987 Nov 17;426(1):93-102
3690322
Eur J Pharmacol. 1998 Jul 10;352(2-3):207-14
9716356
Pharmacol Rep. 2006 Sep-Oct;58(5):652-9
17085857
Epilepsia. 2004 Oct;45(10 ):1176-83
15461671
J Neural Transm Gen Sect. 1992;89(1-2):41-8
1418866
Epilepsy Res. 1997 Jul;28(1):63-72
9255600
Neurosci Res. 1989 Jun;6(5):470-4
2771204
Epilepsia. 1993 Mar-Apr;34(2):385-9
8453947
Epilepsy Res. 1991 Mar;8(2):79-94
2065646
Pharmacol Biochem Behav. 1994 Nov;49(3):609-13
7862714
Seizure. 2004 Jun;13(4):284-5
15121141
Epilepsy Res. 1998 Feb;29(3):233-49
9551785
Epilepsia. 2003 Feb;44(2):150-6
12558567
Epilepsia. 1981 Feb;22(1):85-94
7472302
Epilepsia. 2006 Nov;47(11):1841-54
17116023
Epilepsia. 2004 Aug;45(8):895-907
15270754
J Biol Chem. 1996 Mar 8;271(10):5768-76
8621444
Ann Intern Med. 1975 Jun;82(6):784-7
237450
Neurology. 1975 Sep;25(9):819-22
808758
Mol Pharmacol. 2001 Jan;59(1):144-52
11125035
Eur J Pharmacol. 1987 Dec 15;144(3):309-15
2831068
Epilepsy Res. 1987 Jul;1(4):234-8
3504399
Naunyn Schmiedebergs Arch Pharmacol. 2005 Jul;372(1):41-54
16133488
J Pharmacol Exp Ther. 1949 Jun;96(2):99-113
18152921
Seizure. 2003 Oct;12(7):519-21
12967583
West J Med. 1983 Mar;138(3):371-4
6858124
Epilepsia. 2003 Apr;44(4):489-99
12680997
Eur J Pharmacol. 2007 May 7;562(1-2):53-9
17320861
Pharmacol Rev. 1990 Sep;42(3):223-86
2217531
Epilepsy Behav. 2005 Dec;7(4):639-51
16140589
Neuropharmacology. 2002 Feb;42(2):229-36
11804619