Abstract | PURPOSE: METHODS: The anticonvulsant activity of 5alpha,3alpha-A and 5beta,3alpha-A was investigated in electrical and chemoconvulsant seizure models in mice. The steroids also were examined for activity against extracellularly recorded epileptiform discharges in the CA3 region of the rat hippocampal slice induced by perfusion with 55 microM 4-aminopyridine (4-AP). RESULTS:
Intraperitoneal injection of 5alpha,3alpha-A-protected mice in a dose-dependent fashion from seizures in the following models (ED50, dose in mg/kg protecting 50% of animals): 6-Hz electrical stimulation (29.1), pentylenetetrazol (43.5), pilocarpine (105), 4-AP (215), and maximal electroshock (224). 5beta,3alpha-A also was active in the 6-Hz and pentylenetetrazol models, but was less potent (ED50 values, 76.9 and 139 mg/kg, respectively), whereas epiandrosterone (5alpha,3beta-A) was inactive (ED50, <or=300 mg/kg). 5alpha,3alpha-A (10-100 microM) also inhibited epileptiform discharges in a concentration-dependent fashion in the in vitro slice model, whereas 5beta,3alpha-A was active but of lower potency, and 5alpha,3beta-A was inactive. CONCLUSIONS: 5alpha,3alpha-A and 5beta,3alpha-A have anticonvulsant properties. Although of low potency, the steroids are present in high abundance and could represent endogenous modulators of seizure susceptibility.
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Authors | Rafal M Kaminski, Herbert Marini, Won-Joo Kim, Michael A Rogawski |
Journal | Epilepsia
(Epilepsia)
Vol. 46
Issue 6
Pg. 819-27
(Jun 2005)
ISSN: 0013-9580 [Print] United States |
PMID | 15946323
(Publication Type: Journal Article)
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Chemical References |
- Anticonvulsants
- Pilocarpine
- Testosterone
- Etiocholanolone
- 4-Aminopyridine
- Androsterone
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Topics |
- 4-Aminopyridine
(pharmacology)
- Androsterone
(blood, pharmacology)
- Animals
- Anticonvulsants
(pharmacology)
- Behavior, Animal
(drug effects)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Electroshock
- Epilepsy
(blood)
- Etiocholanolone
(blood, pharmacology)
- Hippocampus
(drug effects, physiopathology)
- Humans
- In Vitro Techniques
- Injections, Intraperitoneal
- Male
- Mice
- Motor Activity
(drug effects)
- Pilocarpine
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Seizures
(chemically induced, physiopathology, prevention & control)
- Testosterone
(blood, metabolism)
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