Animal model for evaluating the convulsive liability of beta-lactam antibiotics.
The beta-lactam antibiotics imipenem-cilastatin, BMY-26225, and cefazolin significantly lowered the convulsive threshold of pentylenetetrazole in mice. In addition, imipenem-cilastatin and cefazolin were found to inhibit 3H-labeled gamma-aminobutyric acid binding to synaptic membranes from rat brains. Our results suggest that the pentylenetetrazole convulsive model may be useful in evaluating the proconvulsive liabilities of new carbapenems and other beta-lactam antibiotics and that the mechanism of imipenem-cilastatin and cefazolin toxicity may involve interaction with gamma-aminobutyric acid receptors.
Williams
P D
PD
Department of Experimental Toxicology, Bristol-Myers Company, Syracuse, New York 13221-4755.
Bennett
D B
DB
Comereski
C R
CR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001667:Binding, Competitive; D002437:Cefazolin / Q000378:metabolism / Q000633:toxicity; D015377:Cilastatin; D000077728:Cilastatin, Imipenem Drug Combination; D003521:Cyclopropanes / Q000378:metabolism / Q000633:toxicity; D004195:Disease Models, Animal; D004338:Drug Combinations / Q000378:metabolism / Q000633:toxicity; D015378:Imipenem; D007769:Lactams; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced*; D013845:Thienamycins / Q000378:metabolism / Q000633:toxicity; D047090:beta-Lactams; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000900:Anti-Bacterial Agents; D003521:Cyclopropanes; D004338:Drug Combinations; D007769:Lactams; D013845:Thienamycins; D047090:beta-Lactams; C056495:BMY 26225; D015377:Cilastatin; D005680:gamma-Aminobutyric Acid; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D002437:Cefazolin; D010433:Pentylenetetrazole; C052467:pyridinium, 2-(((2-carboxy-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo(3.2.0)hept-2-en-3-yl)thio)methyl)-1-methyl-, hydroxide, inner salt, (5R-(5.alpha.,6.alpha.(R*)))-