Biomaterial Database

Deoxycorticosterone's anticonvulsant effects in infant rats are blocked by finasteride, but not by indomethacin. 2006

Claudia Perez-Cruz, and Sergei Likhodii, and W M Burnham

The University of Toronto Epilepsy Research Program and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8. cperez@dpz.gwdg.de

Deoxycorticosterone (DOC) is a steroid hormone that suppresses seizures in both humans and animals. At higher doses, DOC's anticonvulsant actions are accompanied by sedation and ataxia. The mechanism of DOC's anticonvulsant actions is not known, although it has been suggested that they may relate to DOC's secondary metabolite 3-alpha-5-alpha-tetrahydrodeoxycorticosterone (THDOC). The present study was designed to study the relation of DOC's anticonvulsant actions to its primary and secondary metabolites in 15-day-old rats. It was found that DOC's anticonvulsant and ataxic effects were suppressed by finasteride, which blocks the formation of DOC's primary metabolite, 3-alpha-5-alpha-dehydrodeoxycorticosterone (DHDOC). They were not suppressed by indomethacin (INDO), which blocks the conversion of DHDOC into THDOC. The direct anticonvulsant effects of DHDOC and THDOC were also tested. DHDOC and THDOC were both potent anticonvulsants in 15-day old rats. Both also caused ataxia at high doses. DHDOC had a therapeutic index (TI) of 3.2, however, which was better than either DOC (TI = 1.2) or THDOC (TI = 1.5). It appears that DOC itself is not anticonvulsant, but that its anticonvulsant effects may relate to both its primary and secondary metabolites. DOC's primary metabolite, DHDOC--with its good TI--deserves a test in the treatment of childhood seizures.

UI	MeSH Term	Description	Entries
D007213	Indomethacin	A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES.	Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D008297	Male		Males
D010433	Pentylenetetrazole	A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility.	Leptazole,Pentamethylenetetrazole,Pentetrazole,Cardiazol,Corasol,Corazol,Corazole,Korazol,Korazole,Metrazol,Metrazole,Pentazol,Pentylenetetrazol
D003900	Desoxycorticosterone	A steroid metabolite that is the 11-deoxy derivative of CORTICOSTERONE and the 21-hydroxy derivative of PROGESTERONE	21-Hydroxyprogesterone,Cortexone,Deoxycorticosterone,Desoxycortone,11-Decorticosterone,21-Hydroxy-4-pregnene-3,20-dione,11 Decorticosterone,21 Hydroxy 4 pregnene 3,20 dione,21 Hydroxyprogesterone
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D004830	Epilepsy, Tonic-Clonic	A generalized seizure disorder characterized by recurrent major motor seizures. The initial brief tonic phase is marked by trunk flexion followed by diffuse extension of the trunk and extremities. The clonic phase features rhythmic flexor contractions of the trunk and limbs, pupillary dilation, elevations of blood pressure and pulse, urinary incontinence, and tongue biting. This is followed by a profound state of depressed consciousness (post-ictal state) which gradually improves over minutes to hours. The disorder may be cryptogenic, familial, or symptomatic (caused by an identified disease process). (From Adams et al., Principles of Neurology, 6th ed, p329)	Epilepsy, Grand Mal,Epilepsy, Major,Grand Mal Seizure Disorder,Major Motor Seizure Disorder,Seizure Disorder, Tonic Clonic,Convulsions, Grand Mal,Cryptogenic Tonic-Clonic Epilepsy,Epilepsy, Tonic-Clonic, Cryptogenic,Epilepsy, Tonic-Clonic, Familial,Epilepsy, Tonic-Clonic, Symptomatic,Familial Tonic-Clonic Epilepsy,Seizure Disorder, Grand Mal,Seizure Disorder, Major Motor,Symptomatic Tonic-Clonic Epilepsy,Tonic Clonic Convulsions,Tonic-Clonic Convulsion Disorder,Tonic-Clonic Convulsion Syndrome,Tonic-Clonic Seizure Disorder,Tonic-Clonic Seizure Syndrome,Convulsion Disorder, Tonic-Clonic,Convulsion Disorders, Tonic-Clonic,Convulsion Syndrome, Tonic-Clonic,Convulsion Syndromes, Tonic-Clonic,Convulsion, Grand Mal,Convulsion, Tonic Clonic,Convulsions, Tonic Clonic,Cryptogenic Tonic Clonic Epilepsy,Cryptogenic Tonic-Clonic Epilepsies,Disorder, Tonic-Clonic Convulsion,Disorder, Tonic-Clonic Seizure,Disorders, Tonic-Clonic Convulsion,Disorders, Tonic-Clonic Seizure,Epilepsies, Cryptogenic Tonic-Clonic,Epilepsies, Familial Tonic-Clonic,Epilepsies, Symptomatic Tonic-Clonic,Epilepsies, Tonic-Clonic,Epilepsy, Cryptogenic Tonic-Clonic,Epilepsy, Familial Tonic-Clonic,Epilepsy, Symptomatic Tonic-Clonic,Epilepsy, Tonic Clonic,Familial Tonic Clonic Epilepsy,Familial Tonic-Clonic Epilepsies,Grand Mal Convulsion,Grand Mal Convulsions,Grand Mal Epilepsy,Major Epilepsies,Major Epilepsy,Seizure Disorder, Tonic-Clonic,Seizure Disorders, Tonic-Clonic,Seizure Syndrome, Tonic-Clonic,Seizure Syndromes, Tonic-Clonic,Symptomatic Tonic Clonic Epilepsy,Symptomatic Tonic-Clonic Epilepsies,Syndrome, Tonic-Clonic Convulsion,Syndrome, Tonic-Clonic Seizure,Syndromes, Tonic-Clonic Convulsion,Syndromes, Tonic-Clonic Seizure,Tonic Clonic Convulsion,Tonic Clonic Convulsion Disorder,Tonic Clonic Convulsion Syndrome,Tonic Clonic Seizure Disorder,Tonic Clonic Seizure Syndrome,Tonic-Clonic Convulsion Disorders,Tonic-Clonic Convulsion Syndromes,Tonic-Clonic Epilepsies,Tonic-Clonic Epilepsies, Cryptogenic,Tonic-Clonic Epilepsies, Familial,Tonic-Clonic Epilepsies, Symptomatic,Tonic-Clonic Epilepsy,Tonic-Clonic Epilepsy, Cryptogenic,Tonic-Clonic Epilepsy, Familial,Tonic-Clonic Epilepsy, Symptomatic,Tonic-Clonic Seizure Disorders,Tonic-Clonic Seizure Syndromes
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia