Abstract
Fluoroacetic and fluorocitric acid toxicity is often characterized by seizures, however the mechanism of this activity is unknown. Intrathecal (i.t.) injection of fluorocitrate in mice resulted in seizures after an average latency of 15 s, while intracerebroventricular (i.c.v.) injection produced seizures after 36.5 min, and required higher doses to achieve this effect. This indicates the probable site of fluoroacetate and fluorocitrate neurotoxicity is the spinal cord. To mimic citrate accumulation, characteristic of fluoroacetate and fluorocitrate poisoning, critic acid was injected i.t. and also found to produce seizures. The structurally unrelated compounds EDTA, EGTA, glutamic acid and lactic acid also produced seizures identical to fluorocitrate. The ability of these compounds to chelate Ca2+ correlates well with their ability to cause seizures when administered i.t. and coadministration of calcium greatly attenuated the neurotoxicity of these compounds as well as fluoroacetate and fluorocitrate. In contrast, Ca2+ was unable to inhibit seizures elicited by strychnine, suggesting calcium's ability to inhibit chelators of divalent cations is not due to a general anticonvulsant effect. These results suggest that changes in Ca2+ concentration in the spinal cord may be responsible for some forms of seizure activity.
Original language | English (US) |
---|---|
Pages (from-to) | 307-313 |
Number of pages | 7 |
Journal | European Journal of Pharmacology |
Volume | 179 |
Issue number | 3 |
DOIs | |
State | Published - Apr 25 1990 |
Bibliographical note
Funding Information:This work was supported by United States Public Health Service Grants NIDA04090, NIDA04190 and NIDA00124. The authors acknowledge the skillful editorial assistance of Dr. Alvin Beitz, Dr. David Smullin and Dr. Christopher Murray.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.