Effect of topiramate on glucocorticoid receptor mediated action.
This study examined the effects of topiramate (TPM) on glucocorticoid receptors (GRs) in mononuclear leukocytes of nine men and four women with chronic and recurring post-traumatic stress disorder (PTSD) and a group of comparison subjects (nine men, four women). A measure of 60 ml of blood was withdrawn by venipuncture at 0800 and mononuclear leukocytes were isolated. The cells were incubated with a series of concentrations of dexamethasone (DEX) without or with 50 micromol/l of TPM to evaluate the effects of DEX to inhibit lysozyme activity and the effect of TPM on it. ANCOVA compared the IC(50) for lysozyme inhibition under conditions of DEX only and TPM+DEX. TPM affected lysozyme IC(50) in the direction of increasing the sensitivity of the receptor in the sample as a whole. This effect was more pronounced in the mononuclear leukocytes from participants in the PTSD group, particularly in cells from subjects whose pretreatment lysozyme IC(50) was relatively higher (eg, reflecting decreased glucococorticoid receptor responsiveness), compared to the rest of the sample. In conclusion, further investigation of the actions of TPM on GR and other neuroendocrine systems may prove useful in understanding some of the other established clinical effects of this agent.
Yehuda
Rachel
R
The Traumatic Stress Studies Program, Department of Psychiatry, Mount Sinai School of Medicine and the Bronx Veterans Affairs Medical Center, Bronx, NY, USA. rachel.yehuda@med.va.gov
Yang
Ren-Kui
RK
Golier
Julia A
JA
Tischler
Lisa
L
Liong
Betty
B
Decker
Kelly
K
D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001665:Binding Sites; D016022:Case-Control Studies; D003710:Demography; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology*; D013313:Stress Disorders, Post-Traumatic / Q000097:blood / Q000188:drug therapy; D011795:Surveys and Questionnaires; D000077236:Topiramate
D000927:Anticonvulsants; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D000077236:Topiramate; D005632:Fructose; D003907:Dexamethasone; D009113:Muramidase