Effects of Diphenylhydantoin (Dilantin) on Adrenal Cortical Junction

Costa, P. J.; Glaser, Gilbert H.; Bonnycastle, D. D.

doi:10.1001/archneurpsyc.1955.02330130090010

Cited by 15 publications

(2 citation statements)

References 6 publications

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“…After chronic DPH therapy to patients, excretion of corticosteroids in urine is reported to decrease (7,8) after an initial increase (7). These findings have led to the suggestion that the decrease in brain excitability induced by DPH might be mediated partially through adrenocortical suppression.…”

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confidence: 99%

Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

Werk¹,

MacGee²,

Sholiton³

1964

J. Clin. Invest.

166

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During a study of cortisol metabolism in advanced cancer and other disease states (1), we observed in patients receiving DPH 1 therapy for convulsive seizures an abnormal pattern of excretion of cortisol metabolites in urine. This abnormal pattern was characterized by increased urinary output of the polar unconjugated metabolite 6-OHF, suggesting an interference with extraadrenal metabolism of cortisol by DPH. We =5,5'-diphenylhydantoin; 6-hydroxycortisol (6 -OHF) = 6a (/3), 11,/, 17a, 21 -tetrahydroxy -4 -pregnene-3,20 -dione; 17-OHCS = 17-hydroxycorticosteroids; ACTH = adrenocorticotrophic hormone; methopyrapone (Metopirone, Ciba Pharmaceutical Co., Summit, N. J.) =2-methyl-1,2-di-(3-pyridyl)-1-propanone. Tetrahydro derivatives: THF (tetrahydrocortisol) = 3a,11,, 17a,21-tetrahydroxy-5/8-pregnan-20-one; allo-THF (allotetrahydrocortisol) = 3a,11/3,17a,21-tetrahydroxy-5a-?pregnan-20-one; THE (tetrahydrocortisone) = 3a,17a,21-trihydroxy-5p-pregnan-11,20-dione. Cortol = 3a,11,8,17a,20a (/3),21-pentahydroxy-5/3-pregnane; cortolone = 3a,17a,20a (/3) ,21-tetrahydroxy-5/8-pregnan-11-one; 17-KS = 17-ketosteroids; 1 1-hydroxyetiocholanolone = 3a,1j1/-dihydroxy-5,B-androstan-17-one; dehydroisoandrosterone = 3/3-hydroxy-5-androstene-17-one; TPNH = reduced triphosphopyridine nucleotide; o,p'DDD = 2,2-bis (2-chlorophenyl,4-chlorophenyl) 1,1-dichloroethane. since a) adrenal hypertrophy was observed in intact rats and b) in adrenalectomized rats treated with DPH a more profound decrease in brain excitability was demonstrated than in intact rats. Goncharov has observed that acute administration of DPH to dogs and guinea pigs increases adrenocortical output of cortisol (3). Reports by Staple (4) and Bonnycastle and Bradley (5) have, however, indicated an inhibition of pituitary-adrenal secretion after chronic DPH treatment of mice and rats.In humans also cortisol has been shown to enhance brain excitability (6). After chronic DPH therapy to patients, excretion of corticosteroids in urine is reported to decrease (7, 8) after an initial increase (7). These findings have led to the suggestion that the decrease in brain excitability induced by DPH might be mediated partially through adrenocortical suppression. However, levels of 17-OHCS in plasma from patients treated with DPH are usually normal (8, 9), as are responses to ACTH (8, 9) and rates of disappearance from plasma of infused cortisol (8). These observations detract from the possibility that direct adrenocortical suppression plays a significant role in therapeutic effectiveness of DPH. Recently, however, Krieger has demonstrated that control subjects treated with DPH manifest a reduced response in the methopyrapone test, which suggests an interference with ACTH release (10).2) The increased excretion of 6-OHF produced by DPH appears to be similar to that we have observed in patients with advanced cancer and certain terminal illnesses (1) as well as to that reported after estrogen therapy (11), during pregnancy (12), and in newborn infants (13).Thus we hoped that furthe...

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confidence: 99%

Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

Werk¹,

MacGee²,

Sholiton³

1964

J. Clin. Invest.

166

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“…The reduction of adrenocortical function on account of diphenyl hydantoin th erap y has suggested the possible role of this m echanism in the decrease of brain excitability induced by this drug (Costa et al 1955, Bray et al 1954. B ut some authors (Christy and H ofm ann 1959) do not share this view.…”

Section: Discussionmentioning

confidence: 99%

Effect of Diphenylhydantoin Treatment on the Release of Corticotrophin in Epileptic Patients

Rinne¹

1966

Stereotact Funct Neurosurg

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Über die adrenale Steroid‐Biosynthese in vitro. III. Selektive Hemmung der Nebennierenrinden‐Funktion

Kahnt

Neher

1966

Helvetica Chimica Acta

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Volumen 49, Fasciculus 1 (1966) -No. 82-83 725 azides with an hexapeptide. The two latter have been obtained from the hexapeptide by the recurring method, using active trichlorophenyl esters.Comparison of the biological activities of these compounds with those of the corresponding analogues still bearing the a-amino group shows that suppression of this amino group decreases the pressoric/antidiuretic ratio of these compounds.Laboratoires de Chimie pharmaceutique SANDOZ S. A., BAle BIBLIOGRAPHIE

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Effects of Diphenylhydantoin (Dilantin) on Adrenal Cortical Junction

Cited by 15 publications

References 6 publications

Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

Effect of Diphenylhydantoin Treatment on the Release of Corticotrophin in Epileptic Patients

Über die adrenale Steroid‐Biosynthese in vitro. III. Selektive Hemmung der Nebennierenrinden‐Funktion

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