Teratogenic effects of the anticonvulsant gabapentin in mice.
BACKGROUND
We aim to study and elucidate the safety profile of the antiepileptic doses of gabapentin during pregnancy, and to evaluate gabapentin-induced murine fetotoxicity at different dose levels.


METHODS
A total of 60 pregnant mice, divided into 12 groups of five mice each, were exposed to gabapentin in four different doses of 0 (control), 113, 226, or 452 mg/kg body weight per day, at three different gestational stages including early gestation (1-6 days), mid-gestation (7-12 days), and late gestation (13-17 days). The pregnant mice were euthanized on day 18 of gestation, and foetuses were examined for teratogenic manifestations. Their brains were dissected and examined for gross changes, malformations, histological changes, and quantitative protein estimation.


RESULTS
Foetal resorptions were observed in all treated groups with gabapentin administration at early gestation (1-6 days), and mid-gestation (7-12 days). On the other hand, growth retardation along with stunting in size of live foetuses were observed in all the mid-gestation (7-12 days), and late gestation (13-17 days) treated groups. Various gross malformations were observed with all the three doses (113, 226, and 452 mg/kg body weight per day) when gabapentin was administered at mid-gestation (7-12 days). The same trends were confirmed by gross and microscopic examination of brains along with quantitative protein estimation.


CONCLUSIONS
Gabapentin should not be prescribed during pregnancy, as no therapeutic dose of gabapentin is safe during this period as far as the foetal well-being is concerned.
Prakash
Department of Anatomy, Kasturba Medical College, Mangalore, Karnataka 575004, India. prakashrinku@rediffmail.com
Prabhu
L V
LV
Rai
R
R
Pai
M M
MM
Yadav
S K
SK
Madhyastha
S
S
Goel
R K
RK
Singh
G
G
Nasar
M A
MA
D000014:Abnormalities, Drug-Induced; D000588:Amines / Q000009:adverse effects*; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D001835:Body Weight; D000013:Congenital Abnormalities / Q000517:prevention & control; D003509:Cyclohexanecarboxylic Acids / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D000077206:Gabapentin; D051379:Mice; D008813:Mice, Inbred ICR; D008956:Models, Chemical; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects; D013723:Teratogens; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects*
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D013723:Teratogens; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin