Abstract | PURPOSE: METHODS: the effect of acute systemic administration of safranal on latency to seizure onset as well as spike and wave discharches (SWD) duration following pharmacologically-induced absence seizures was investigated in wildtype mice. We further characterized its effects on the GABAergic system through the regional modification of [3H] flunitrazepam, a benzodiazepine agonist binding site and [3H] CGP54626A, a GABAB receptor antagonist binding site in mouse brain. RESULTS: The systemic administration of safranal resulted in a significant and dose-dependent attenuation in experimental absence seizures elicited by either gamma-butyrolactone (GBL), baclofen (BAC) or low doses of GABAA receptor antagonists; pentylenetetrazole (PTZ), picrotoxin (PTX) and bicuculline (BMC). After a single intraperitoneal administration of safranal (291 mg/kg), no changes in baseline electrocorticographic (ECoG) recording were observed, however, a significant decrease in [3H] flunitrazepam binding was seen in the cortex (33.16%, p<0.001), hippocampus (27.36%, p<0.01) and thalamus (29.91%, p<0.01) of mouse brain, while the [3H] CGP54626A binding did not show any modification in the same brain regions. CONCLUSION: These data indicate that there is an antiabsence seizure property in safranal and its effect may be due to modifications on the benzodiazepine binding sites of the GABAA receptor complex.
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Authors | Hamid R Sadeghnia, Miguel A Cortez, Dick Liu, Hossein Hosseinzadeh, O Carter Snead 3rd |
Journal | Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
(J Pharm Pharm Sci)
Vol. 11
Issue 3
Pg. 1-14
( 2008)
ISSN: 1482-1826 [Electronic] Canada |
PMID | 18801302
(Publication Type: Journal Article)
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Chemical References |
- Cyclohexenes
- Receptors, GABA-A
- Terpenes
- safranal
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Topics |
- Animals
- Autoradiography
(methods)
- Binding Sites
- Brain
(drug effects, metabolism)
- Crocus
(chemistry)
- Cyclohexenes
(administration & dosage, isolation & purification, pharmacology)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Electroencephalography
(methods)
- Epilepsy, Absence
(drug therapy, physiopathology)
- Injections, Intraperitoneal
- Male
- Mice
- Mice, Inbred C57BL
- Receptors, GABA-A
(metabolism)
- Terpenes
(administration & dosage, isolation & purification, pharmacology)
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