TERATOGENIC EFFECT OF AMITRIPTYLIN AND AMINEPTINE ANTIDEPRESSANTS: AN EXPERIMENTAL STUDY ON ALBINO RATS
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Teratogenecity of amitriptyline and amineptine antidepressants was investigated in pups of sixty dams. They were divided into three equal groups. The first group was served as control. The 2nd and 3rd groups were treated orally, by gavage, with daily therapeutic doses of amitriptyline (0.0054 mg/gm b. w.) and amineptine (0.009 mg/gm b.w.) respectively from the first day of gestation till the end of pregnancy. On the 20111 day of gestation, ten dams from each group were sacrificed and their uteri and pups were examined. The remaining ten dams in each group were left to complete their pregnancy and their pups were examined and followed up for four weeks. Data obtained revealed significant decrease of live pups and increase of resorped and dead fetuses among the treated groups versus control group. Data also revealed significant retardation of growth indices for pups of treated groups versus control pups. Amitriptyline produced 19.26% and 15.54% decrease in mean birth weight and length respectively, while amineptine produced 31.27% and 27.42% decrease respectively. Growth retardation in the first four weeks after birth was manifested by 19.16% and 27.95% decrease in mean weight gain per day, and 21.18% and 25.88% decrease in mean length gain per day for groups 11 and HI respectively versus controls. Significant increase of morphological anomalies was found among pups of treated dams. lit groups II and III respectively, the morphological anomalies included kinked tail (20% and 34.8%), flat occiput (12.7% and 19.6%), multiple haemorrhagic areas (5.5% and 13%), thin translucent skin (3.6% and 17.4%). and absent digits of forefeet (5.5% and 13%) and hindfeet (7.3% and 15.2%). Absent one or both eyes was detected in three pups of group III, 2-4 weeks after birth. Skeletal anomalies demonstrated by Alizarin technique among pups of groups 11 and HI respectively, included incomplete ossification of cranial bones (10% and 35%), ribs and sternum (10% and 30%), and unossified carpal bones (20% and 30%), metacarpal bones (20% and 40%), phalanges of forefeet (25% and 35%), tarsal bones (20% and 20%), metatarsal bones (15% and 25%), phalanges of hindfeet (25% and 40%), coccegeal vertebrae (40% and 45%) and lumber vertebrae (5% and 20%). Histopathological changes were found in the skin and internal organs of pups of treated dams. Data of the present study proved the teratogenic potential risk of amitriply- line and amineptine antidepressants in Albino rats and it is recommended that these drugs should not be prescribed during pregnancy.