Neurotoxicity of Intravenously Administered Penicillin G

Penicillin G, 20 million units daily given intravenously to a nonuremic patient, caused encephalopathy (progressive restlessness, confusion, hallucinations, and multifocal myoclonus) followed by recovery after discontinuation of the drug. In normal awake cats doses up to 1.3 million units/ kg produced encephalopathy with myoclonus; higher doses culminated in status epilepticus and death. Pretreatment with small doses minimized the effects of a subsequent high dose. In awake rats 4.5 to 5 million units/kg produced encephalopathy resulting in death of the majority of animals. In rats anesthetized with ether, same results were obtained with 3 to 3.5 million units/kg. The highest concentrations of labeled penicillin G in brain, located mostly in membranal-nuclear fraction, was reached in five to ten minutes. The penicillin encephalopathy was reversed in animals by intravenously administered penicillinase.