Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluoxetine, a selective serotonin reuptake inhibitor, is known to increase the cortical content of allopregnanolone (ALLO) without altering the level of other neurosteroids. In contrast to the proconvulsant effect of many antidepressants, fluoxetine exhibits anticonvulsant effects. The present study was undertaken to examine the role of ALLO in the anticonvulsant action of fluoxetine against pentylenetetrazole (PTZ)-induced seizures in mice. Prior administration of GABA(A) receptor agonist muscimol or neurosteroid ALLO or progesterone, a precursor of ALLO or neurosteroidogenic drugs like FGIN 1-27, an agonist at the mitochondrial diazepam binding inhibitor receptor (MDR) or metyrapone, an 11beta-hydroxylase inhibitor, significantly potentiated the anticonvulsant effect of fluoxetine. In contrast, the effect of fluoxetine was counteracted by inhibition of the neurosteroid biosynthesis using drugs like 5alpha-reductase inhibitor, finasteride; 3beta-hydroxysteroid dehydrogenase inhibitor, trilostane; 3alpha-hydroxysteroid dehydrogenase inhibitor, indomethacin; MDR antagonist, PK 11195; or the GABA(A) receptor antagonist, bicuculline. Further, bilateral adrenalectomy had no significant effect on the anticonvulsant action of fluoxetine, suggesting negligible contribution from peripheral steroidogenesis. The anticonvulsant effect of fluoxetine was partially abolished in 5,7-DHT treated mice, indicating that the effect may also, in part, be dependent on serotonergic transmission. Thus, our data indicate that increased synthesis of ALLO in CNS is a major factor that ultimately leads to anticonvulsant effects of fluoxetine against PTZ-induced seizures.
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PMID:Essentiality of central GABAergic neuroactive steroid allopregnanolone for anticonvulsant action of fluoxetine against pentylenetetrazole-induced seizures in mice. 1536 24

Steroid hormones, such as progestogens and androgens, influence seizures. Progestogens and androgens exert organizational and/or activational effects that may mitigate vulnerability to, and/or expression of, some seizure disorders. Progestogens, such as progesterone (P(4)) and its 5alpha-reduced metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), which vary across the reproductive cycle and lifespan, may protect against seizures through actions at intracellular progestin receptors (PRs) and membrane receptors, such as gamma-aminobutyric acid (GABA)(A) receptors. Similarly, androgens, such as testosterone (T), which also vary across the reproductive cycle and the lifespan, can have antiseizure effects. Some of these effects of T may be due to aromatization to estrogen and/or 5alpha-reduction to dihydrotestosterone (DHT), and its subsequent conversion through 3alpha-hydroxysteroid dehydrogenase to 5alpha-androstane-3alpha,17alpha-diol (3alpha-diol). Sensitivity to steroids in some individuals may be mitigated by differences in stress, developmental phase, reproductive status, endocrine status, and treatments, such as antiepileptic drugs (AEDs), which alter levels of these ligands and/or function of their target sites. The evidence implicating sex steroids in differences associated with hormonal, reproductive, developmental, stress, seizure type, and/or therapeutics are discussed.
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PMID:Effects and mechanisms of progestogens and androgens in ictal activity. 2061 19