[Neurotoxicity of carbapenem compounds and other beta-lactam antibiotics].
The neurotoxic potencies are considerably different among various beta-lactam antibiotics. Some carbapenem antibiotics, a new class beta-lactam antibiotic, also induce convulsion in human and laboratory animals. This article reviews the structure activity relationship for the neurotoxicity of beta-lactam antibiotics, especially carbapenems. As for the neurotoxicity of carbapenem antibiotics, the presence of amino group in the C-2 side chain is an important factor in inducing convulsion and the strength of basicity of the amino group is correlated with the convulsant activity. The beta-lactam ring of carbapenem is not necessary to evoke convulsions. The neurotoxicity of carbapenem antibiotics is related to only a part of the structure, including the C-2 side chain, but not to the carbapenem skeleton itself. In comparison with other beta-lactam antibiotics, it has been found that the structure responsible for the convulsive action of carbapenems is significantly different from penicillins and cephalosporins in which the beta-lactam ring is essential to evoke convulsion. The induction of convulsions by carbapenem antibiotics is predominantly caused through the inhibition of gamma aminobutyric acid receptor in a similar manner as with penicillins and cephalosporins. However, the detail mechanism may be different not only among carbapenems, cephalosporins, and penicillins but among carbapenem compounds themselves. It is important to know the neurotoxic potential of a compound by investigating the effect of direct administration into the central nervous system such as intraventricular administration, since the penetration through blood-brain barrier or the pharmacokinetic property is varied in seriously ill patients. Possible drug interactions regarding neurotoxicity are also discussed. We hope these findings described here will be helpful in developing more efficient and safer beta-lactam antibiotics of a new generation.
Sunagawa
M
M
Sumitomo Pharmaceuticals Research Center.
Nouda
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001921:Brain / Q000187:drug effects*; D015780:Carbapenems / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D015780:Carbapenems