Anticonvulsant actions of deoxycorticosterone.
OBJECTIVE
Adrenocorticotrophic hormone (ACTH) suppresses several types of childhood seizures, but it has many side effects. The mechanism of ACTH's anticonvulsant actions is not known. ACTH, however, releases deoxycorticosterone (DOC) - as well as cortisol - from the adrenal cortex and it has been suggested that DOC may mediate, at least in part, ACTH's anticonvulsant actions. The present study assessed DOC's anticonvulsant actions in infant rats. Age-related changes in DOC's anticonvulsant actions were also studied.


METHODS
DOC's anticonvulsant actions were assessed against hippocampal-kindled, maximal pentylenetetrazol test (MMT) and maximal electroshock (MES) seizures in 15-day-old rats. Age-related changes in responsiveness to DOC were also assessed using the MMT model.


RESULTS
DOC suppressed generalized convulsions in all three of the seizure models. Focal spiking in the hippocampal-kindling model, however, was not fully suppressed, even at high doses. Ataxia increased proportionally with the dose, with the time of peak seizure suppression roughly correlating with the time of peak ataxia in all models. DOC was anticonvulsant in both infant and adult rats. ED50s, however, were much higher in adults. Young rats showed ataxia at the time of testing (15 min), whereas adult rats did not, although ataxia was seen at later times.


CONCLUSIONS
DOC is a potent anticonvulsant against generalized seizures, particularly in infants. It deserves a clinical test against generalized seizures in infants.
Perez-Cruz
Claudia
C
The University of Toronto Epilepsy Research Program and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Lonsdale
Deborah
D
Burnham
W McIntyre
WM
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology / Q000627:therapeutic use; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001259:Ataxia / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D003292:Convulsants / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology* / Q000627:therapeutic use; D004558:Electric Stimulation / Q000009:adverse effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D016896:Treatment Outcome
D000927:Anticonvulsants; D003292:Convulsants; D003900:Desoxycorticosterone; D000324:Adrenocorticotropic Hormone