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Epileptogenic activity of some β-lactam derivatives: Structure-activity relationship

Authors
Journal
Neuropharmacology
0028-3908
Publisher
Elsevier
Publication Date
Volume
28
Issue
4
Identifiers
DOI: 10.1016/0028-3908(89)90030-0
Keywords
  • Seizures
  • Penicillins
  • Cephalosporins
  • Aztreonam
  • Epilepsy

Abstract

Abstract The epileptogenic activity of several derivatives of β-lactam was compared following their intracerebroventricular administration in rats. At a dose of 0.033 μmol/kg cefazolin was the most powerful epileptogenic compound among the drugs tested; dramatic seizure signs (nodding, clonic convulsions and sometimes escape responses) were observed repeatedly. It was approximately three times more potent than benzylpenicillin and other similar compounds, such as ceftriaxone, cefoperazone and cefamandole. No epileptogenic signs were observed with equimolar doses of cefotaxime, cefonicid and ceftizoxime. All these derivatives differ from the substitution at position 3 and at position 7 of 7-aminocephalosporanic acid. The more convulsant compounds (i.e. cefazolin and ceftezole) are both derivatives of tetrazol and show a marked similarity with pentylentetrazol. In addition, aztreonam, a compound having only the β-lactam ring substituted with a heterocyclic ring at the 4 position, possessed convulsant properties like those of cefoperazone and cefamandole. This suggests that the β-lactam ring is able to produce epileptogenic activity and it seems likely that substitutions at the 7-aminocephalosporanic or 6-aminopenicillanic acid may increase or reduce the epileptogenic properties of β-lactam derivatives.

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