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Open AccessArticle

Paradoxical Anticonvulsant Effect of Cefepime in the Pentylenetetrazole Model of Seizures in Rats

Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Toreza Prospekt 44, 194223 Saint Petersburg, Russia
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Pharmaceuticals 2020, 13(5), 80; https://doi.org/10.3390/ph13050080
Received: 24 March 2020 / Revised: 22 April 2020 / Accepted: 24 April 2020 / Published: 26 April 2020
(This article belongs to the Section Pharmacology)
Many β-lactam antibiotics, including cephalosporins, may cause neurotoxic and proconvulsant effects. The main molecular mechanism of such effects is considered to be γ-aminobutyric acid type a (GABAa) receptor blockade, leading to the suppression of GABAergic inhibition and subsequent overexcitation. We found that cefepime (CFP), a cephalosporin, has a pronounced antiepileptic effect in the pentylenetetrazole (PTZ)-induced seizure model by decreasing the duration and severity of the seizure and animal mortality. This effect was specific to the PTZ model. In line with findings of previous studies, CFP exhibited a proconvulsant effect in other models, including the maximal electroshock model and 4-aminopyridine model of epileptiform activity, in vitro. To determine the antiepileptic mechanism of CFP in the PTZ model, we used whole-cell patch-clamp recordings. We demonstrated that CFP or PTZ decreased the amplitude of GABAa receptor-mediated postsynaptic currents. PTZ also decreased the current decay time constant and temporal summation of synaptic responses. In contrast, CFP slightly increased the decay time constant and did not affect summation. When applied together, CFP prevented alterations to the summation of responses by PTZ, strongly reducing the effects of PTZ on repetitive inhibitory synaptic transmission. The latter may explain the antiepileptic effect of CFP in the PTZ model. View Full-Text
Keywords: epilepsy; antibiotic-induced seizures; animal models of seizures; pentylenetetrazole; Cefepime; GABAa receptor; IPSC epilepsy; antibiotic-induced seizures; animal models of seizures; pentylenetetrazole; Cefepime; GABAa receptor; IPSC
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Amakhin, D.V.; Smolensky, I.V.; Soboleva, E.B.; Zaitsev, A.V. Paradoxical Anticonvulsant Effect of Cefepime in the Pentylenetetrazole Model of Seizures in Rats. Pharmaceuticals 2020, 13, 80.

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