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September 1971

Neurotoxicity of Intravenously Administered Penicillin G

Author Affiliations

New York
From the Department of Neurology, Cornell University Medical College, New York. Dr. Raichle is now at the US Air Force School of Aerospace Medicine, Brooks Air Force Base, Tex.

Arch Neurol. 1971;25(3):232-239. doi:10.1001/archneur.1971.00490030058006

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.

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