Therapeutic Efficacy of Δ5-Pregnenolone in Rheumatoid Arthritis

Freeman, H. C.

doi:10.1001/jama.1950.02910330006003

Cited by 21 publications

(4 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this pilot study, we thus investigated pregnenolone as an adjunctive therapeutic strategy for cognitive and negative symptoms in patients with schizophrenia or schizoaffective disorder with an escalating fixed-dose approach, achieving a total dose of 500 mg/day (approaching the highest well tolerated dose reported in the existing literature) in the last 4 weeks of the study administered in divided doses (Freeman et al , 1950b; McGavack et al , 1951). Although human pharmacokinetic studies addressing acute administration are extremely few, a single oral dose of pregnenolone 175 mg approximately doubles serum levels over the course of 4–8 h (Roberts, 1995).…”

Section: Introductionmentioning

confidence: 99%

Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia

Marx

Keefe

Boyer

et al. 2009

Neuropsychopharmacol

163

158

View full text Add to dashboard Cite

The neurosteroid pregnenolone and its sulfated derivative enhance learning and memory in rodents. Pregnenolone sulfate also positively modulates NMDA receptors and could thus ameliorate hypothesized NMDA receptor hypofunction in schizophrenia. Furthermore, clozapine increases pregnenolone in rodent hippocampus, possibly contributing to its superior efficacy. We therefore investigated adjunctive pregnenolone for cognitive and negative symptoms in patients with schizophrenia or schizoaffective disorder receiving stable doses of second-generation antipsychotics in a pilot randomized, placebo-controlled, double-blind trial. Following a 2-week single-blind placebo lead-in, patients were randomized to pregnenolone (fixed escalating doses to 500 mg/day) or placebo, for 8 weeks. Primary end points were changes in BACS and MCCB composite and total SANS scores. Of 21 patients randomized, 18 completed at least 4 weeks of treatment (n = 9/group). Pregnenolone was well tolerated. Patients receiving pregnenolone demonstrated significantly greater improvements in SANS scores (mean change = 10.38) compared with patients receiving placebo (mean change = 2.33), p = 0.048. Mean composite changes in BACS and MCCB scores were not significantly different in patients randomized to pregnenolone compared with placebo. However, serum pregnenolone increases predicted BACS composite scores at 8 weeks in the pregnenolone group (rs = 0.81, p = 0.022). Increases in allopregnanolone, a GABAergic pregnenolone metabolite, also predicted BACS composite scores (rs = 0.74, p = 0.046). In addition, baseline pregnenolone (rs = −0.76, p = 0.037), pregnenolone sulfate (rs = − 0.83, p = 0.015), and allopregnanolone levels (rs = −0.83, p = 0.015) were inversely correlated with improvements in MCCB composite scores, further supporting a possible role for neurosteroids in cognition. Mean BACS and MCCB composite scores were correlated (rs = 0.74, p <0.0001). Pregnenolone may be a promising therapeutic agent for negative symptoms and merits further investigation for cognitive symptoms in schizophrenia.

show abstract

Section: Introductionmentioning

confidence: 99%

Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia

Marx

Keefe

Boyer

et al. 2009

Neuropsychopharmacol

163

158

View full text Add to dashboard Cite

show abstract

“…pituitary adrenocorticotropic hormone (ACTH) 7 to be sure the pretreatment temperature was consistent. Eleven patients were observed with parenterally administered cortisone, and ten with ACTH.…”

Section: Methodsmentioning

confidence: 99%

“…Several steroids have been recommended for treating rheumatoid arthritis: delta-5-pregnenolone (7), testosterone (8), 21-acetoxypregnenolone (Artisone) (9), and others. Some of these were identified only by number as their structural formulae and chemical names had not been revealed at the time of study.…”

Section: Effect Of Parenteral Acth and Cortisonementioning

confidence: 99%

Joint Temperature Measurement in the Evaluation of Anti-Arthritic Agents 12

Hollander¹,

Stoner²,

Brown³

et al. 1951

J. Clin. Invest.

View full text Add to dashboard Cite

“…These doses were chosen following careful review of prior dosing strategies in the existing literature that were tolerated without significant side 105–107 . Although human pharmacokinetic studies are very few, a single dose of pregnenolone 175 mg appears to approximately double serum pregnenolone levels over the course of 5–8 h; estimated half‐life 8–12 h, and pregnenolone levels decrease by approximately 60% with age, 108 we anticipate that our dosing strategy of 500 mg in the last 4 weeks of the protocol will produce pregnenolone levels that are approximately threefold of those observed in young adulthood in most study subjects.…”

Section: Project 3: Randomized Placebo‐controlled Trial Of Pregnenolomentioning

confidence: 99%

The Singapore flagship programme in translational and clinical research in psychosis

Chong

Campbell

Chee

et al. 2011

Early Intervention in Psychiatry

View full text Add to dashboard Cite

show abstract

Therapeutic Efficacy of Δ5-Pregnenolone in Rheumatoid Arthritis

Cited by 21 publications

References 7 publications

Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia

Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia

Joint Temperature Measurement in the Evaluation of Anti-Arthritic Agents 12

The Singapore flagship programme in translational and clinical research in psychosis

Contact Info

Product

Resources

About