INFLUENCE OF INTRACEREBROVENTRICULAR ADMINISTRATION OF TETANUS TOXIN ON EXPERIMENTAL SEIZURES AND PROTECTION AFFORDED BY SOME ANTIEPILEPTIC DRUGS IN MICE

The dose of the intracerebroventricularly administered (i.c.v.) tetanus toxin (Tetx) evoking the death of 50% of experimental mice (LD50) was estimated to be 18.0 (11.5–28.2) times the minimal lethal dose (MLD). MLD is defined as the lowest dose of Tetx necessary to kill a 20-g albino mouse within 9...

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Bibliographic Details
Published in:Pharmacological research 1998-06, Vol.37 (6), p.477-483
Main Authors: KOROLKIEWICZ, R., MLYNARCZYK, M., GASIOR, M., KLEINROK, Z.
Format: Article
Language:English
Subjects:
Animals
Anticonvulsants - blood
Anticonvulsants - therapeutic use
Brain - drug effects
Brain - metabolism
Convulsants - pharmacology
Drug Synergism
gamma-Aminobutyric Acid - metabolism
Glutamate Decarboxylase - metabolism
Injections, Intraventricular
Lethal Dose 50
Male
Mice
Seizures - chemically induced
Seizures - prevention & control
Tetanus Toxin - administration & dosage
tetanus, electroshock, pentylenetetrazole, bicuculline, aminophylline, pilocarpine
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Summary:The dose of the intracerebroventricularly administered (i.c.v.) tetanus toxin (Tetx) evoking the death of 50% of experimental mice (LD50) was estimated to be 18.0 (11.5–28.2) times the minimal lethal dose (MLD). MLD is defined as the lowest dose of Tetx necessary to kill a 20-g albino mouse within 96 h after intraperitoneal treatment. Tetx (0.25 and 0.5 LD50) increased the convulsive threshold of electric current from 24 to 96 and 120 h, respectively, following i.c.v. administration. Both doses of Tetx diminished convulsant potencies of pentylenetetrazole, bicuculline, aminophylline and pilocarpine 24 h after application. At the same time Tetx (0.5 LD50) increased the protection afforded by carbamazepine, valproate, phenobarbital and diazepam in maximal electroshock (MES) by approximately 36, 11, 21 and 26%, respectively, without affecting total blood plasma levels of antiepileptic drugs. No marked changes in γ-aminobutyric acid (GABA) concentration and total activity ofl-glutamic acid decarboxylase (GAD) assessed in the whole-brain homogenates resulted from Tetx treatment. Our results seem to indicate that low doses (
ISSN:1043-6618
1096-1186
DOI:10.1006/phrs.1998.0317