BioMed Research International

Research Article

Teratogenic Potential of Antiepileptic Drugs in the Zebrafish Model

Table 1

Malformation effects of antiepileptic drugs on zebrafish.


	Embryo numbers ()			Malformation in embryos ()
	Treated	Lethal (%)	Normal (%)	Observed	Head	Tail	Heart	Yolk	Scoliosis	Growth retardation¹	Teratogenicity

Carbamazepine
2 mM	10	10 (100%)	—	0	—	—	—	—	—	—	—
1 mM	16	12 (75%)	0 (0%)	4	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	4 (100%)	4 (100%)
0.5 mM	19	10 (53%)	1 (11%)	9	0 (0%)	0 (0%)	4 (44%)	0 (0%)	1 (11%)	6 (67%)	8 (89%)
0.25 mM	10	2 (20%)	5 (50%)	8	0 (0%)	0 (0%)	2 (25%)	0 (0%)	0 (0%)	1 (13%)	3 (38%)
0.1 mM	20	7 (35%)	9 (45%)	13	0 (0%)	1 (8%)	3 (23%)	0 (0%)	1 (8%)	2 (15%)	4 (31%)

Lacosamide
10 mM	14	7 (50%)	0 (0%)	7	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	7 (100%)	7 (100%)^b
5 mM	26	14 (54%)	2 (8%)	12	0 (0%)	2 (17%)	7 (58%)	0 (0%)	4 (33%)	3 (25%)	10 (83%)^b
2.5 mM	10	3 (30%)	3 (30%)	7	0 (0%)	0 (0%)	1 (14%)	0 (0%)	0 (0%)	3 (43%)	4 (57%)^b
1 mM	26	5 (19%)	16 (62%)	21	0 (0%)	1 (5%)	1 (5%)	0 (0%)	1 (5%)	3 (14%)	5 (24%)
0.5 mM	25	4 (16%)	20 (80%)	21	0 (0%)	1 (5%)	1 (5%)	0 (0%)	1 (5%)	1 (5%)	2 (10%)^a

Lamotrigine
1 mM	25	5 (20%)	7 (28%)	20	1 (5%)	1 (5%)	8 (40%)	6 (30%)	7 (35%)	5 (25%)	13 (65%)^b
0.5 mM	25	6 (24%)	10 (40%)	19	1 (5%)	2 (11%)	4 (21%)	5 (26%)	2 (11%)	2 (11%)	9 (47%)
0.25 mM	15	2 (13%)	12 (80%)	13	0 (0%)	1 (8%)	0 (0%)	1 (8%)	0 (0%)	0 (0%)	1 (8%)
0.1 mM	25	9 (36%)	12 (48%)	16	0 (0%)	0 (0%)	3 (19%)	2 (13%)	0 (0%)	0 (0%)	4 (25%)
0.05 mM	25	9 (36%)	16 (64%)	16	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)^a

Topiramate
50 mM	10	8 (80%)	0 (0%)	2	0 (0%)	0 (0%)	2 (100%)	2 (100%)	1 (50%)	1 (50%)	2 (100%)
10 mM	16	10 (63%)	4 (25%)	6	0 (0%)	0 (0%)	2 (33%)	1 (17%)	2 (33%)	1 (17%)	2 (33%)
5 mM	15	3 (20%)	5 (33%)	12	0 (0%)	0 (0%)	4 (33%)	1 (8%)	1 (8%)	3 (25%)	7 (58%)
1 mM	14	5 (36%)	3 (21%)	9	0 (0%)	0 (0%)	6 (67%)	2 (22%)	2 (22%)	2 (22%)	6 (67%)
0.5 mM	15	3 (20%)	9 (60%)	12	0 (0%)	1 (8%)	3 (25%)	0 (0%)	0 (0%)	0 (0%)	3 (25%)

Ethosuximide
100 mM	15	15 (100%)	—	0	—	—	—	—	—	—	—
50 mM	15	9 (60%)	2 (0%)	6	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	4 (67%)	4 (67%)
10 mM	15	7 (47%)	1 (7%)	8	0 (0%)	0 (0%)	7 (88%)	0 (0%)	0 (0%)	6 (75%)	7 (88%)
5 mM	15	6 (40%)	9 (60%)	9	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
1 mM	15	6 (40%)	9 (60%)	9	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)

Levetiracetam
100 mM	14	6 (43%)	7 (50%)	8	0 (0%)	1 (13%)	0 (0%)	0 (0%)	0 (0%)	1 (13%)	1 (13%)
50 mM	15	6 (40%)	9 (60%)	9	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
10 mM	10	5 (50%)	5 (50%)	5	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
5 mM	15	6 (40%)	9 (60%)	9	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
1 mM	15	7 (47%)	7 (47%)	8	0 (0%)	0 (0%)	1 (13%)	0 (0%)	0 (0%)	0 (0%)	1 (13%)

Valproic acid
100 M	12	12 (100%)	—	0	—	—	—	—	—	—	—
50 M	20	3 (15%)	4 (20%)	17	—	—	—	—	—	13 (76%)	13 (76%)^b
25 M	20	2 (10%)	1 (5%)	18	—	—	—	—	—	17 (94%)	17 (94%)^b
12.5 M	20	3 (15%)	13 (65%)	17	—	—	—	—	—	4 (24%)	4 (24%)^a
6.25 M	20	3 (15%)	15 (75%)	17	—	—	—	—	1 (5%)	2 (12%)	2 (12%)^a

1% DMSO	28	2 (7%)	26 (93%)	28	0 (0%)	0 (0%)	1 (4%)	0 (0%)	1 (4%)	0 (0%)	2 (7%)

1: including unhatched embryo at 72 hours post-fertilization.
“—” Indicated the numbers not determined.
^a,bDifferent characters indicate significant difference within drugs (<0.05).