High ambient pressure of 41 bar increases the cerebral toxicity of penicillins.

Sodium benzylpenicillin, cloxacillin, and azlocillin were infused intravenously in awake rats at 1 and 41 bar until they convulsed. The doses necessary to elicit convulsions were significantly lower at 41 than at 1 bar, i.e., with a 24% (P less than 0.0005) lower dose of benzylpenicillin and a 23% lower dose of azlocillin (P less than 0.005). The convulsion threshold of cloxacillin was also lower (13%), but not statistically significant. The results show that high pressure reduces the convulsion threshold for some penicillins. Hippocampal amino acid concentrations were also measured in animals exposed to 1 and 41 bar with and without benzylpenicillin treatment. Infusion of benzylpenicillin at 1 bar led to a decrease of 15% in the glutamate level (P less than 0.05), whereas at 41 bar it decreased the level of glutamate by 17% (P less than 0.05) as well as that of glutamine by 19% (P less than 0.05). The results suggest that treatment with penicillin at high ambient pressure may increase the turnover of transmitter glutamate in the rat hippocampus and thus increase the excitability. These effects should be considered when high doses of penicillins are administered to man at high ambient pressure.