Sedation or Seizures as Dose-Dependent Effects of Steroids

Heuser, G. F.; Ling, George M.; Buchwald, N.A.

doi:10.1001/archneur.1965.00470020085012

Cited by 34 publications

(4 citation statements)

References 24 publications

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“…7-keto DHEA would also have a distinct advantage over DHEA as a treatment for alcohol abuse and dependence in that it does not act as a precursor for the sex hormones (Lardy et al , 1998) and would be free of the adverse effects associated with increased production of testosterone and estradiol (Panjari and Davis, 2007). Furthermore, unlike the sulfated form of DHEA (DHEA-S) (Ticku and Kulkarni, 1988) and the negative modulator RO15-4513 (Karp et al , 2009), there is very little evidence that DHEA (Heuser et al , 1965) or 7-keto DHEA are proconvulsant unless administered in large concentrations directly into the brain. In contrast, RO15-4513 has been shown to be convulsant in rats at relatively high doses, and a study by Miczek and Weerts (1987) found that small doses of this compound (1 mg/kg) in primates produced overt seizure-related behaviors (e.g., tremors) including a fatal tonic-clonic seizure in one subject.…”

Section: Discussionmentioning

confidence: 99%

A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

Amato¹,

Hulin²,

Winsauer³

2012

Behavioural Pharmacology

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Dehydroepiandrosterone (DHEA), 7-keto DHEA, and several comparison drugs (ethanol, chlordiazepoxide, rauwolscine, and RO15-4513) were administered to male rats responding under a multiple schedule of food and ethanol presentation to determine their selectively for decreasing ethanol-maintained responding. DHEA and 7-keto DHEA significantly decreased both ethanol- and food-maintained responding, compared to control, while also decreasing blood ethanol concentration (BEC). Acute ethanol administration also decreased responding for both food and ethanol; however, ethanol-maintained responding was more potently decreased than food-maintained responding. BEC remained relatively stable after increasing ethanol doses. Among the other drugs tested, RO15-4513 was the most selective for decreasing ethanol-maintained responding compared to food-maintained responding, and it decreased BECs as ethanol-maintained responding decreased. The largest dose of rauwolscine significantly decreased responding for food, while not affecting ethanol-maintained responding compared to control. Low to intermediate doses of rauwolscine produced small, non-significant increases in ethanol-maintained responding and BECs. Chlordiazepoxide produced significant decreases in food-maintained responding and the dose of ethanol presented, but only at the highest dose tested. Although DHEA and 7-keto DHEA did not decrease ethanol-maintained responding as selectively as ethanol or RO15-4513 under the multiple schedule, these neurosteroids may be valuable pharmacological tools in the development of new treatments for alcohol abuse and dependence.

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Section: Discussionmentioning

confidence: 99%

A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

Amato¹,

Hulin²,

Winsauer³

2012

Behavioural Pharmacology

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“…[47] In animal seizure models, pregnenolone sulfate and DHEAS have proconvulsant effect. [48] Of note, serum DHEAS levels are substantially reduced by enzymeinducing antiepileptic drugs (AED) such as phenytoin and carbamazepine. [49,50] Hormonal Treatment…”

Section: Neurosteroidsmentioning

confidence: 99%

Current Concepts of Catamenial Epilepsy

Herzog¹

2016

Epilepsi

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Seizures do not occur randomly. They tend to cluster in the majority of men and women with epilepsy. Seizure clusters, in turn, often show a temporal periodicity. When the periodicity of seizure exacerbation aligns itself with that of the menstrual cycle, it is designated catamenial epilepsy. The neuroactive properties of reproductive steroids and the cyclic variation in their serum concentrations are important pathophysiologic factors. There is evidence for the existence of at least 3 patterns of catamenial seizure exacerbation: perimenstrual and periovulatory in ovulatory cycles, and entire luteal phase in anovulatory cycles. A rational mathematical basis for this categorization of catamenial epilepsy has been developed. It identifies over one-third of women as having catamenial epilepsy. If seizures show hormonal sensitivity in their occurrence, they may also respond to hormonal treatment. A randomized, double-blind, placebo-controlled National Institute of Health (NIH) progesterone trial found that cyclic progesterone supplement is no better than placebo overall, but did reduce seizure frequency significantly in the subset of women with perimenstrual seizure exacerbation. There have also been successful open-label trials using depomedroxyprogesterone and depot gonadotropin-releasing hormone analogues.

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“…47 In animal seizure models, pregnenolone sulfate and DHEAS have proconvulsant effect. 48 Of note, serum DHEAS levels are substantially reduced by enzyme-inducing antiepileptic drugs such as phenytoin and carbamazepine. 49,50 Hormonal treatment…”

Section: Neurosteroidsmentioning

confidence: 99%

Catamenial epilepsy: Definition, prevalence pathophysiology and treatment

Herzog

2008

Seizure

186

141

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Seizures do not occur randomly. They tend to cluster in the majority of men and women with epilepsy. Seizure clusters, in turn, often show a periodicity. When the periodicity of seizure exacerbation aligns itself with that of the menstrual cycle, it is designated as catamenial epilepsy. The neuroactive properties of reproductive steroids and the cyclic variation in their serum concentrations are important pathophysiologic factors. Recent investigations have demonstrated and confirmed the existence of at least three patterns of catamenial seizure exacerbation: perimenstrual and periovulatory in ovulatory cycles and entire luteal phase in anovulatory cycles. A rational mathematical basis for the categorization of seizure exacerbation as catamenial epilepsy has been developed. It identifies approximately one third of women as having catamenial epilepsy. If seizures show hormonal sensitivity in their occurrence, they may also respond to hormonal treatment. Successful open label trials using cyclic natural progesterone supplement, depomedroxyprogesterone and gonadotropin-releasing hormone analogues in women and using testosterone with or without aromatase inhibitor in men have been reported. Prospective, randomized, placebo-controlled, double-blind investigations are warranted and under way.

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Sedation or Seizures as Dose-Dependent Effects of Steroids

Cited by 34 publications

References 24 publications

A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

Current Concepts of Catamenial Epilepsy

Catamenial epilepsy: Definition, prevalence pathophysiology and treatment

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