Minocycline- and tetracycline-class antibiotics are protective against partial seizures in vivo.

Wang DD, Englot DJ, Garcia PA, Lawton MT, Young WL
Epilepsy Behav. 2012 24 (3): 314-8

PMID: 22579030 · PMCID: PMC3761078 · DOI:10.1016/j.yebeh.2012.03.035

INTRODUCTION - Increasing evidence suggests the role of inflammation in enhancing neuronal excitability and contributing to epileptogenesis. Tetracycline-class antibiotics minocycline, doxycycline and tetracycline have been shown to have anti-apoptotic and anti-inflammatory effects.

METHODS - We investigated the anti-seizure effects of tetracycline-class antibiotics minocycline, doxycycline and tetracycline in vivo by using the maximal electric shock (MES), 6-Hz (minimal clonic seizure) test and subcutaneous Metrazol (scMET) models of epilepsy.

RESULTS - Minocycline, doxycycline and tetracycline showed anticonvulsant effects in abolishing partial seizures in the mouse 6-Hz seizure test. A dose-dependent effect was found, with ED(50) of 170 mg/kg for minocycline, 157 mg/kg for doxycycline, and 255 mg/kg for tetracycline with peak onset at 0.5h. At high doses, minocycline (250 mg/kg) and doxycycline (150 mg/kg) also had toxic effects, from motor impairments to respiratory failure and death. These drugs had no effects on the MES and scMET tests.

CONCLUSIONS - In the three tests of anti-seizure activity, minocycline, doxycycline, and tetracycline were found to be protective in one: the 6-Hz seizure model. Our data suggest that minocycline and other tetracycline-class drugs may offer some degree of anticonvulsant effect in the setting of CNS disease trials.

Published by Elsevier Inc.

MeSH Terms (14)

Animals Anti-Bacterial Agents Anticonvulsants Dose-Response Relationship, Drug Doxycycline Epilepsies, Partial Male Mice Minocycline Neurons Rats Rats, Sprague-Dawley Seizures Tetracycline

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