A comparative study on the convulsant activity of carbapenems and beta-lactams.
Beta-lactams are well known to have potent convulsant activity. Imipenem, the first carbapenem antibiotic introduced in the clinical field, has been reported to induce convulsions. The neurochemical mechanism of the convulsions induced by carbapenems and cephalosporins were studied. Intraventricular injection of cefazolin, cephaloridine and imipenem, and of panipenem (a new carbapenem), induced convulsions in a dose-dependent manner in mice. They inhibited the receptor binding of gamma-aminobutyric acid (GABA), an inhibitory transmitter in the mammalian central nervous system. These in-vitro and in-vivo results suggest that carbapenems and cephalosporins might induce convulsions through the inhibition of GABA receptor binding when they are accumulated in the central nervous system.
Shimada
J
J
Division of Clinical Pharmacology, St. Marianna University School of Medicine, Kawasaki, Japan.
Hori
S
S
Kanemitsu
K
K
Shoji
Y
Y
Nakashio
S
S
Yanagawa
A
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D013570:Synaptic Membranes / Q000187:drug effects
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002511:Cephalosporins; D011963:Receptors, GABA-A