ABSTRACT

Introduction: Tramadol belongs to the group of quasi-narcotic compounds and is used as an analgesic drug with central effects in the treatment of moderate-to-severe acute pain (after surgery and trauma) and chronic cancer pain, and chronic non‐cancer pain, for example, due to osteoarthritis. Tramadol is a weak μ-opioid receptor agonist and its analgesic activity is mainly based on serotonin reuptake inhibition. This drug is a weak reuptake inhibitor of norepinephrine. It is contraindicated in patients with a history of seizure disorders, and its use increases serotonin syndrome. Due to the occurrence of fetal complications, in this study, the probability of the teratogenic effects of tramadol on the mice embryo was investigated.

Method: Pregnant mice were fed a tramadol dose of 1-3-9-27-50-100 mg/kg during the 7th to 9th day of pregnancy, and were anesthetized with isoflurane on the 15th day of pregnancy. The fetuses were removed to assess the number of miscarriages, fetal and placental weights, fetal length and placental diameter, liver size and uterine diameter, and histopathological examination, and were studied for developmental toxicity.

Results: The results of statistical analysis showed that tramadol significantly reduced fetal weight and fetal length after exposure to 1-3-9-27-50-100 mg/kg concentrations. However, at a dose of 27 mg/kg, fetal weight and length did not change significantly. The weight of the placenta increased significantly at a dose of 27 mg/kg, and the weight and diameter of the placenta decreased significantly at a dose of 100 mg/kg, and there was a significant increase in uterine horn diameter and endometrial thickness compared to the control group. Also, histopathological examination showed that tramadol causes skeletal anomalies and pathological disorders in the brain, liver, abdominal wall, and placenta.

Conclusion: As a result of the research, the use of tramadol during pregnancy causes anomalies in fetal development and histopathological changes in the process of brain and liver development. Therefore, it is recommended to be careful in taking this drug during pregnancy.

Keywords: Tramadol, Anomaly, Embryonic-Fetal Toxicity, Developmental Toxicity,mousefetus