Abstract
Abstract
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French
Recently, there has been an increase in the research devoted to the study of investigational antiepileptic medications. This has led to extensive clinical trials of several new compounds. This review focuses on four of these antiepileptic medications in development: felbamate, gabapentin, lamotrigine, and vigabatrin. Each has a unique mechanism of action and great potential for the treatment of epilepsy.
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References
1.
Porter
RJ
Cereghino
JJ
Gladding
GD
Antiepileptic drug development program . Cleve Clin J Med
1984 ; 51 : 293 –305 .
2.
Leppik
IE
Dreifuss
FE
Porter
RJ
A controlled study of progabide in partial seizures: Methodology and results . Neurology
1987 ; 37 : 963 –8 .
3.
Porter
RJ
. Mechanisms of action of new antiepileptic drugs . Epilepsia
1989 ; 30 (suppl ):S29 –S34 .
4.
Meldrum
BS
. Pharmacologic approaches to the treatment of epilepsy . In:
Meldrum
BS
Porter
RJ
, eds. New anticonvulsant drugs . London : John Libbey , 1986 : 17 –30 .
5.
Meldrum
BS
. GABAergic mechanisms in the pathogenesis and treatment of epilepsy . Br J Clin Pharmacol
1989 ; 27 (suppl ):3s –11s .
6.
Loscher
W
Schmidt
D
. Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations . Epilepsy Res
1988 ; 2 : 145 –81 .
7.
Meldrum
BS
. Preclinical test systems for evaluation of novel compounds . In:
Meldrum
BS
Porter
RJ
, eds. New anticonvulsant drugs . London : John Libbey , 1986 : 31 –48 .
8.
Leppik
IE
Graves
NM
. Potential antiepileptic drugs: Felbamate . In:
Levy
R
Mattson
R
Meldrum
B
Penry
JK
Dreifuss
FE
, eds. Antiepileptic drugs . 3rd ed . New York : Raven Press , 1989 : 983 –90 .
9.
Swinyard
EA
Sofia
RD
Kupferberg
HJ
. Comparative anticonvulsant activity and neurotoxicity of felbamate and four prototype antiepileptic drugs in mice and rats . Epilepsia
1986 ; 27 : 27 –34 .
10.
Perhach
JL
Weliky
I
Newton
JJ
Sofia
RD
Romanyshyn
WM
Arndt
WF
. Felbamate . In:
Meldrum
BS
Porter
RJ
, eds. New anticonvulsant drugs . London : John Libbey , 1986 : 117 –23 .
11.
Wilensky
AJ
Friel
PN
Ojemann
LM
Kupferberg
HJ
Levy
RH
. Pharmacokinetics of W-554 (ADD03055) in epileptic patients . Epilepsia
1985 ; 26 : 602 –6 .
12.
Graves
NM
Ludden
TM
Holmes
GB
Fuerst
RH
Leppik
IE
. Pharmacokinetics of felbamate, a novel antiepileptic drug: Application of mixed-effect modeling to clinical trials . Pharmacotherapy
1989 ; 9 : 372 –6 .
13.
Sheridan
PH
Ashworth
M
Milne
K
Open pilot study of felbamate (ADD03055) in partial seizures (abstract) . Epilepsia
1986 ; 27 : 649 .
14.
Graves
NM
Holmes
GB
Fuerst
RH
Leppik
IE
. Effect of felbamate on Phenytoin and carbamazepine serum concentrations . Epilepsia
1989 ; 30 : 225 –9 .
15.
Graves
NM
Remmel
RP
Miller
S
The effect of felbamate on the major metabolites of carbamazepine (abstract) . Pharmacotherapy
1989 ; 9 : 196 .
16.
Wagner
ML
Graves
NM
Marienau
K
Holmes
GB
Remmel
RP
Leppik
IE
. Discontinuation of phenytoin and carbamazepine in patients receiving felbamate . Epilepsia
1991 ; 32 : 398 –406 .
17.
Leppik
IE
Dreifuss
FE
Pledger
GW
Et
AL
. Felbamate in partial seizures: Resultó of Phase II clinical trial (abstract) . Epilepsia
1989 ; 30 : 661 .
18.
Leppik
IE
Kramer
LD
Bourgeoise
B
Graves
NM
Campbell
J
Cruz-Rodrigues
R
. Felbamate after withdrawal from other antiepileptic drugs (abstract) . Neurology
1990 ; 40 : 158 .
19.
Theodore
WH
Raubertas
R
Porter
RJ
Felbamate: A double-blind placebo-controlled three-period crossover trial (abstract) . Epilepsia
1989 ; 30 : 661 .
20.
Schmidt
B
. Potential antiepileptic drugs: Gabapentin . In:
Levy
R
Mattson
R
Meldrum
B
Penry
JK
Dreifuss
FE
, eds. Antiepileptic drugs . 3rd ed . New York : Raven Press , 1989 : 925 –35 .
21.
Bartoszyk
GD
Meyerson
N
Reimann
W
Satzinger
G
Vonhodenberg
A
. Gabapentin . In:
Meldrum
BS
Porter
RJ
, eds. New anticonvulsant drugs . London : John Libbey , 1986 : 147 –63 .
22.
Graves
NM
Holmes
GB
Leppik
IE
Pharmacokinetics of gabapentin in patients treated with phenytoin (abstract) . Pharmacotherapy
1989 ; 9 : 196 .
23.
Saletu
B
Grunberger
J
Linzmayer
L
. Evaluation of encephalotropic and psychotropic properties of gabapentin in man by pharmaco-EEG and psychometry . Int J Clin Pharmacol Ther Toxicol
1986 ; 24 : 362 –73 .
24.
Rao
ML
Clarenback
P
Vahlensieck
M
Kratzschmar
S
. Gabapentin augments whole blood serotonin in healthy young men . J Neural Transm
1988 ; 73 : 129 –34 .
25.
Crawford
P
Ghadiali
E
Lane
R
Blumhardt
L
Chadwick
D
. Gabapentin as an antiepileptic drug in man . J Neurol Neurosurg Psychiatry
1987 ; 50 : 682 –6 .
26.
Miller
AA
Sawyer
DA
Roth
B
Lamotrigine . In:
Meldrum
BS
Porter
RJ
, eds. New anticonvulsant drugs . London : John Libbey , 1986 : 165 –77 .
27.
Gram
L
. Potential antiepileptic drugs: Lamotrigine . In:
Levy
R
Mattson
R
Meldrum
B
Penry
JK
Dreifuss
FE
, eds. Antiepileptic drugs . 3rd ed . New York : Raven Press , 1989 : 947 –53 .
28.
Binnie
CD
Beintema
CJ
Debets
RMC
Seven day administration of lamotrigine in epilepsy: Placebo-controlled add-on trial . Epilepsy Res
1987 ; 1 : 202 –8 .
29.
Jawad
S
Richens
A
Goodwin
G
Yuen
WC
. Controlled trial of lamotrigine (Lamictal) for refractory partial seizures . Epilepsia
1989 ; 30 : 356 –63 .
30.
Lewis
P
. Introduction . Br J Clin Pharmacol
1989 ; 27 (suppl ):1S .
31.
Butler
WH
. The neuropathology of vigabatrin . Epilepsia
1989 ; 30 (suppl ):S15 –7 .
32.
Pauärvi
L
Vapalahti
M
Sivenius
J
Riekkinen
P
. Vigabatrin vacuoles in humans: Neuropathologic findings in 5 patients with vigabatrin treatment (abstract) . Neurology
1990 ; 40 (suppl ): 157 .
33.
Richens
A
. Potential antiepileptic drugs; vigabatrin . In:
Levy
R
Mattson
R
Meldrum
B
Penry
JK
Dreifuss
FE
, eds. Antiepileptic drugs . 3rd ed . New York : Raven Press , 1989 : 937 –46 .
34.
Schechter
PJ
. Clinical pharmacology of vigabatrin . Br J Clin Pharmacol
1989 ; 27 (suppl ):19S –22S .
35.
Browne
TR
Mattson
RH
Penry
JK
A multicentre study of vigabatrin for drug-resistant epilepsy . Br J Clin Pharmacol
1989 ; 27 (suppl ):95S –100S .
36.
Frisk-Holmberg
M
Kerth
P
Meyer
PH
. Effect of food on the absorption of vigabatrin . Br J Clin Pharmacol
1989 ; 27 (suppl ):23S –5S .
37.
Rimmer
EM
Richens
A
. Double blind study of gamma-vinyl GABA in patients with refractory epilepsy . Lancet
1984 ; 1 : 189 –90 .
38.
Browne
TR
Mattson
RH
Penry
JK
Vigabatrin for refractory complex partial seizures: Multicentre single blind study with long term follow-up . Neurology
1987 ; 37 : 184 –9 .
39.
Rimmer
EM
Richens
A
. Interaction between vigabatrin and phenytoin . Br J Clin Pharmacol
1989 ; 27 (suppl ):27S –33S .
40.
Gram
L
. Experimental studies and controlled clinical testing of valproate and vigabatrin . Acta Neurol Scand
1988 ; 78 : 241 –70 .
41.
Ben-Menachem
E
Persson
LL
Schechter
PJ
The effect of different vigabatrin treatment regimens on CSF biochemistry and seizure control in epileptic patients . Br J Clin Pharmacol
1989 ; 27 (suppl ):79S –85S .
42.
Gram
L
Lyon
Blatt B
Dam
M
. Gamma-vinyl-GABA: A single blind trial in patients with epilepsy . Acta Neurol Scand
1983 ; 68 : 34 –9 .
43.
Schecter
PJ
Hanke
NFJ
Grove
J
Huebert
N
Sjoerdsma
A
. Biochemical and clinical effects of gamma-vinyl-GABA in patients with epilepsy . Neurology
1984 ; 34 : 182 –6 .
44.
Gram
L
Klosterkov
P
Dam
M
. Gamma-vinyl GABA: A double-blind placebo-controlled trial in partial epilepsy . Ann Neurol
1985 ; 17 : 262 –6 .
45.
Loiseau
P
Berg
Harden JP
Pestre
M
Guyot
M
Schechter
PJ
Tell
GP
. Double-blind placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy . Epilepsia
1986 ; 27 : 115 –20 .
46.
Tartara
A
Manni
R
Galimberti
CA
Hardenberg
J
Orwin
J
Perucca
E
. Vigabatrin in the treatment of epilepsy: A double-blind placebo-controlled study . Epilepsia
1986 ; 27 : 717 –23 .
47.
Tassinari
CA
Michelucci
R
Ambrosetoo
G
Salvi
F
. Double-blind study of vigabatrin in the treatment of drug-resistant epilepsy . Arch Neurol
1987 ; 44 : 907 –10 .
48.
Luna
D
Dulac
O
Pajot
N
Beaumont
D
. Vigabatrin in the treatment of childhood epilepsies: A single blind placebo-controlled study . Epilepsia
1989 ; 30 : 430 –7 .
49.
Livingston
JH
Beaumont
D
Arzimanoglou
A
Aicardi
J
. Vigabatrin in the treatment of epilepsy in children . Br J Clin Pharmacol
1989 ; 27 (suppl ):109S –12S .
50.
Tartara
A
Manni
R
Galimberti
CA
Mumford
JP
Ludice
A
Perucca
E
. Vigabatrin in the treatment of epilepsy: A long-term follow-up study . J Neurol Neurosurg Psychiatry
1989 ; 52 : 467 –71 .
