Background: Pregabalin (PGB) has been an anti-epileptic and an effective treatment of 
neuropathic pain; it acts by inhibiting certain presynaptic calcium channels and decreased 
excitatory neurotransmitters. There are reported serious effects following PGB exposure beside 
its addictive effect. Aim of the work: Study the pattern of acute PGB toxicity in patients 
admitted to Poison Control Center-Ain Shams University Hospitals (PCCASUH) and its 
histopathological effects after acute toxic dose in adult albino rat brain.
Methods: The study was comprised of two parts. The clinical part: on 31 patients admitted to 
PCCASUH with a history of acute PGB toxicity. The experimental part: on thirty adult albino 
rats, divided into two groups (acute toxicity group received acute single dose of PGB5000 mg/kg 
and the control group received normal saline). Results: Acute PGB exposure leads to mild 
toxicity and most of symptoms related to CNS included DCL, with a significant relation between 
the prolonged period of hospital admission and the DCL. The experimental results revealed that 
the cerebral cortex (CC) and cerebellum showed degeneration of nerve cells, pyknosis with 
karyolysis of nuclei, and a marked increase in the glial cells with positive glial fibrillary acidic 
protein (GFAP) cytoplasmic granules in the CC (toxic group). Conclusion: The course of PGB 
intoxication is mostly mild self-limiting and most of patients discharged on the next day of 
admission. The experimental study concluded that PGB has degenerative effects on brain nerve 
cells. Recommendations: further studies with larger sample size to evaluate the acute and 
chronic toxicity of PGB. 
Received in original form: 15 January 2023 Accepted in final form: 31 January 2023