Repeated treatment with quinolones potentiates the seizures induced by aminophylline in genetically epilepsy-prone rats

Sarro, Angela De; Trimarchi, Giuseppe; Ammendola, D.; Sarro, Giovambattista De

doi:10.1016/0306-3623(92)90237-e

Cited by 9 publications

(5 citation statements)

References 40 publications

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“…Previous studies have shown the prevalent role of GABAergic deficit in the inferior colliculus and auditory pathway of the GEPR and in the auditory seizure activity predisposition [92,93]. Subsequent studies demonstrated an important role mediated by excitatory neurotransmitters [94][95][96][97] as well as by calcium conductance [98]. Other studies have shown that NA and 5-HT deficits contribute primarily to the generalized seizure susceptibility in GEPRs [99][100][101][102][103][104].…”

Section: Seizures In Geprsmentioning

confidence: 93%

Genetically epilepsy-prone rats (GEPRs) and DBA/2 mice: Two animal models of audiogenic reflex epilepsy for the evaluation of new generation AEDs

Sarro¹,

Russo²,

Citraro³

et al. 2017

Epilepsy & Behavior

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Section: Seizures In Geprsmentioning

confidence: 93%

Genetically epilepsy-prone rats (GEPRs) and DBA/2 mice: Two animal models of audiogenic reflex epilepsy for the evaluation of new generation AEDs

Sarro¹,

Russo²,

Citraro³

et al. 2017

Epilepsy & Behavior

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“…Thus, it appears questionable that a specific interaction of quinolones with the GABA receptor can alone explain the proconvulsant activity of these compounds (17). Indeed, in contrast to the GABAergic mechanism, some authors suggested that other receptors, such as opioid and excitatory amino acid receptors, may also be involved in CNS effects of quinolones (1,13,16,18,30,37). Therefore, a GABAergic mechanism is thought to be an essential part of but not the sole component of the mechanism by which quinolones induce seizures; glutamate is also suspected of being involved (1,13,37).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, in contrast to the GABAergic mechanism, some authors suggested that other receptors, such as opioid and excitatory amino acid receptors, may also be involved in CNS effects of quinolones (1,13,16,18,30,37). Therefore, a GABAergic mechanism is thought to be an essential part of but not the sole component of the mechanism by which quinolones induce seizures; glutamate is also suspected of being involved (1,13,37). Furthermore, recent studies have clearly shown that compounds which antagonize ionotropic glutamate receptors inhibit quinolone-induced seizures in mice; therefore, it was suggested that it is most likely that excessive activation of glutamate receptors occurs secondarily to or concomitantly with the impairment of the inhibitory GABAergic neurotransmission caused by quinolones and that it is essential for the propagation of seizures (1,15,37).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, convulsions have been reported more frequently for individuals predisposed to epileptic seizures and for patients who have received both fluoroquinolones and either theophylline or certain nonsteroidal anti-inflammatory drugs (3,7,21,24,31). In previous studies, members of our team described a convulsant behavioral pattern following the concomitant administration of quinolones and theophylline in a particular strain of rats, namely, genetically epilepsy-prone rats (11,13). In addition, members of our team demonstrated that quinolones potentiate the convulsant effects elicited by cefazolin or imipenem in mice (12,14).…”

mentioning

confidence: 99%

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Effects of Novel 6-Desfluoroquinolones and Classic Quinolones on Pentylenetetrazole-Induced Seizures in Mice

Sarro

Cecchetti

Fravolini

et al. 1999

Antimicrob Agents Chemother

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There have been several reports that convulsions, although rare, occur in patients who receive fluoroquinolones. In this study, the proconvulsant effects exhibited by a novel series of 6-desfluoroquinolones and some classic quinolones on pentylenetetrazole (PTZ)-induced seizures in mice were evaluated and compared. Animals were intraperitoneally injected with vehicle or quinolone derivatives (5 to 100 μg/g of body weight) 30 min before the subcutaneous (s.c.) administration of PTZ (40 μg/g). In each experiment, mice were then observed for 1 h to monitor for the incidence and onset of clonic seizures. The order of proconvulsant activity in our epileptic model was MF5184 > MF5187 > pefloxacin > MF5189 > ofloxacin > ciprofloxacin > MF5140 > MF5181 > MF5137 > rufloxacin > MF5143 > MF5158 > MF5191 > MF5128 > MF5138 > cinoxacin > MF5142 > norfloxacin > nalidixic acid. The relationship between the chemical structure and the proconvulsant activity of 6-desfluoroquinolone derivatives was studied. We observed that, in terms of toxicity to the central nervous system (CNS), besides the heterocyclic side chain (moiety) at the C-7 position, the C-6 substituent also appears to play an important role. In particular, a hydrogen at the C-6 position seemed to be responsible for major neurotoxic activity in comparison to an amino group located in the same position. The relationship between lipophilicity and proconvulsant activity was also investigated. We did not find any clear relationship between a higher level of lipophilicity and major proconvulsant properties. Although the principal mechanism by which quinolones induce potentiation of the proconvulsant effects of PTZ cannot be easily determined, it is possible that the convulsions are caused by drug interactions, because both PTZ and quinolones are believed to increase excitation of the CNS by inhibition of γ-aminobutyric acid binding to receptors.

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“…Although recently developed quinolones are less toxic than earlier compounds, they still produce a very few incidences of various adverse effects on the central nervous system such as dizziness, headache, seizures, and hallucinations (2,17,20,25,26). We have previously reported the proconvulsant effects of several quinolones when administered together with aminophylline in rats and with ␤-lactam derivatives in mice (9)(10)(11)(12). The convulsant actions of quinolones have been attributed to the inhibition of ␥-aminobutyric acid (GABA) binding to its receptor (1,31,39,41).…”

mentioning

confidence: 99%

Effects of some excitatory amino acid antagonists and drugs enhancing gamma-aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice

Sarro

Nava

Calapai

et al. 1997

Antimicrob Agents Chemother

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The behavioral and convulsant effects of pefloxacin (PEFLO), a quinolone derivative, were studied after intraperitoneal (i.p.) administration to Dilute Brown Agouti DBA/2J (DBA/2) mice, a strain genetically susceptible to sound-induced seizures. The anticonvulsant effects of some excitatory amino acid (EAA) antagonists acting at N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptors and of some compounds enhancing gamma-aminobutyric acid (GABA)-ergic transmission against seizures induced by PEFLO were also evaluated. The present study demonstrated that both groups of compounds administered i.p. or intracerebroventricularly were able to protect against seizures induced by PEFLO. However, ifenprodil and (+/-)-alpha-(chlorophenyl)-4-[(4-fluorophenyl)methyl]-1-piperidine-ethan ol (SL 82.0715), two compounds acting on the polyamine site of the NMDA receptor complex, were unable to provide any protection. The relationship between the different sites of action and the anticonvulsant activities of these derivatives were discussed. Although the main mechanisms of PEFLO-induced seizures cannot be easily determined, potential interactions with the receptors of EAA exist. In fact, antagonists of EAA, and in particular, those acting at NMDA receptors, were able to increase the threshold for the seizures or to prevent the seizures induced by PEFLO, while compounds acting at the polyamine site did not provide any protection. The AMPA-KA receptor antagonists were also able to exert anticonvulsant activity, but with minor potency in comparison to those of NMDA antagonists. In addition, the fact that compounds enhancing GABA-ergic neurotransmission were also able to protect the mice against seizures induced by PEFLO suggests an involvement of GABA system.

show abstract

Repeated treatment with quinolones potentiates the seizures induced by aminophylline in genetically epilepsy-prone rats

Cited by 9 publications

References 40 publications

Genetically epilepsy-prone rats (GEPRs) and DBA/2 mice: Two animal models of audiogenic reflex epilepsy for the evaluation of new generation AEDs

Genetically epilepsy-prone rats (GEPRs) and DBA/2 mice: Two animal models of audiogenic reflex epilepsy for the evaluation of new generation AEDs

Effects of Novel 6-Desfluoroquinolones and Classic Quinolones on Pentylenetetrazole-Induced Seizures in Mice

Effects of some excitatory amino acid antagonists and drugs enhancing gamma-aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice

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