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. 1988 May;32(5):758–760. doi: 10.1128/aac.32.5.758

Animal model for evaluating the convulsive liability of beta-lactam antibiotics.

P D Williams 1, D B Bennett 1, C R Comereski 1
PMCID: PMC172267  PMID: 3395104

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barza M. Imipenem: first of a new class of beta-lactam antibiotics. Ann Intern Med. 1985 Oct;103(4):552–560. doi: 10.7326/0003-4819-103-4-552. [DOI] [PubMed] [Google Scholar]
  2. Bechtel T. P., Slaughter R. L., Moore T. D. Seizures associated with high cerebrospinal fluid concentrations of cefazolin. Am J Hosp Pharm. 1980 Feb;37(2):271–273. [PubMed] [Google Scholar]
  3. Calandra G. B., Brown K. R., Grad L. C., Ahonkhai V. I., Wang C., Aziz M. A. Review of adverse experiences and tolerability in the first 2,516 patients treated with imipenem/cilastatin. Am J Med. 1985 Jun 7;78(6A):73–78. doi: 10.1016/0002-9343(85)90104-4. [DOI] [PubMed] [Google Scholar]
  4. Curtis D. R., Game C. J., Johnston G. A., McCulloch R. M., MacLachlan R. M. Convulsive action of penicillin. Brain Res. 1972 Aug 11;43(1):242–245. doi: 10.1016/0006-8993(72)90288-0. [DOI] [PubMed] [Google Scholar]
  5. Gebhart R. J., Duma R. J., Patterson P. M., Bagett J. W., Williams D. S. Primaxin in the treatment of acute bacterial pneumonia in adults. J Antimicrob Chemother. 1985 Feb;15(2):233–238. doi: 10.1093/jac/15.2.233. [DOI] [PubMed] [Google Scholar]
  6. Gerald M. C., Massey J., Spadaro D. C. Comparative convulsant activity of various penicillins after intracerebral injection in mice. J Pharm Pharmacol. 1973 Feb;25(2):104–108. doi: 10.1111/j.2042-7158.1973.tb10602.x. [DOI] [PubMed] [Google Scholar]
  7. Hori S., Kurioka S., Matsuda M., Shimada J. Inhibitory effect of cephalosporins on gamma-aminobutyric acid receptor binding in rat synaptic membranes. Antimicrob Agents Chemother. 1985 Apr;27(4):650–651. doi: 10.1128/aac.27.4.650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kamei C., Sunami A., Tasaka K. Epileptogenic activity of cephalosporins in rats and their structure-activity relationship. Epilepsia. 1983 Aug;24(4):431–439. doi: 10.1111/j.1528-1157.1983.tb04913.x. [DOI] [PubMed] [Google Scholar]
  9. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  10. Park S. Y., Parker R. H. Review of imipenem. Infect Control. 1986 Jun;7(6):333–337. doi: 10.1017/s0195941700064377. [DOI] [PubMed] [Google Scholar]
  11. Raichle M. E., Kutt H., Louis S., McDowell F. Neurotoxicity of intravenously administered penicillin G. Arch Neurol. 1971 Sep;25(3):232–239. doi: 10.1001/archneur.1971.00490030058006. [DOI] [PubMed] [Google Scholar]
  12. Rotiroti D., de Sarro G. B., Musolino R., Nisticò G. A new model of experimental epilepsy: the cefazolin-induced epilepsy. Prog Clin Biol Res. 1983;124:129–144. [PubMed] [Google Scholar]
  13. SWINYARD E. A., BROWN W. C., GOODMAN L. S. Comparative assays of antiepileptic drugs in mice and rats. J Pharmacol Exp Ther. 1952 Nov;106(3):319–330. [PubMed] [Google Scholar]
  14. Yost R. L., Lee J. D., O'Leary J. P. Convulsions associated with sodium cefazolin: a case report. Am Surg. 1977 Jun;43(6):417–420. [PubMed] [Google Scholar]
  15. Zukin S. R., Young A. B., Snyder S. H. Gamma-aminobutyric acid binding to receptor sites in the rat central nervous system. Proc Natl Acad Sci U S A. 1974 Dec;71(12):4802–4807. doi: 10.1073/pnas.71.12.4802. [DOI] [PMC free article] [PubMed] [Google Scholar]

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