- |||||||||| Esmya (ulipristal acetate) / ASKA Pharma, HRA Pharma, Gedeon Richter, AbbVie, sepranolone (UC1010) / Asarina Pharma
Review, Journal: GABA-ergic Modulators: New Therapeutic Approaches to Premenstrual Dysphoric Disorder. (Pubmed Central) - Aug 21, 2023
We then reflect on the implications of these therapeutic advances, including how they may promote our knowledge of affective regulation more generally. We conclude that these and other studies of PMDD may yield critical insight into the etiopathogenesis of affective disorders, considering that (1) symptoms in PMDD have a predictable onset and offset, allowing for examination of affective state kinetics, and (2) GABAergic interventions in PMDD can be used to better understand the relationship between mood states, network regulation, and the balance between excitatory and inhibitory signaling in the brain.
- |||||||||| progesterone / Generic mfg.
Alterations in Progesterone Metabolism Underlie Postpartum Depression (Sapphire AB) - Apr 29, 2023 - Abstract #SOBP2023SOBP_445;
Using a generalized linear mixed-effects model and repeated measures of PPD, adjusting for postpartum week, age, sleep quality, gestational age, and psychiatric medication use, we found, in women who were not depressed at T3, decreased pregnanolone and increased progesterone were associated with PPD and lower pregnanolone to progesterone levels and higher isoallopregnanolone to pregnanolone ratios were associated with PPD. Conclusions A higher level of progesterone and corresponding lower levels of progesterone metabolites in T3 were associated with the later development of PPD, indicating that altered progesterone metabolism may underlie the vulnerability to PPD in some women.
- |||||||||| sepranolone (UC1010) / Asarina Pharma
Neuroactive Steroid Levels in the First Trimester of Pregnancy Are Higher in Those With Perinatal-Emergent Depression (Sapphire AB) - Apr 29, 2023 - Abstract #SOBP2023SOBP_130;
Linear regression models assessed the association between history of depression and current T1 depression status with T1 levels of 4 NAS: allopregnanolone (ALLO), isoallopregnanolone (ISO), pregnanolone (PA), and epipregnanolone (EPI), covarying for BMI, number of prior pregnancies, Medicaid status, relationship status, and income...Conclusions T1 NAS may be blunted in those with persistent depression pre-pregnancy and in pregnancy, but heightened in those with perinatal-emergent T1 depression. The role of NAS in early perinatal depression may depend on history of depression in low-income women of color.
- |||||||||| sepranolone (UC1010) / Asarina Pharma
Journal: Acute stress impairs sensorimotor gating via the neurosteroid allopregnanolone in the prefrontal cortex. (Pubmed Central) - Dec 20, 2022
These effects were reversed by isoallopregnanolone (isoAP), an endogenous AP antagonist, and the GABA receptor antagonist bicuculline and mimicked by AP infusions in the medial prefrontal cortex (mPFC)...These results collectively indicate that acute stress impairs PPI by increasing AP content in the mPFC. The confirmation of these mechanisms across distinct animal models and several acute stressors strongly supports the translational value of these findings and warrants future research on the role of AP in information processing.
- |||||||||| sepranolone (UC1010) / Asarina Pharma
Journal: Gut Steroids and Microbiota: Effect of Gonadectomy and Sex. (Pubmed Central) - Jul 2, 2022
We noted that a number of taxa and inferred metabolic pathways were associated with gut steroids, such as positive associations between Blautia with T, dihydroprogesterone (DHP), and allopregnanolone (ALLO), whereas negative associations were noted between Roseburia and T, ALLO, PREG, ISOALLO, DHP, and PROG. In conclusion, this study highlights the novel sex-specific association between microbiota and gut steroids with possible relevance for the gut-brain axis.
- |||||||||| Esmya (ulipristal acetate) / ASKA Pharma, HRA Pharma, Gedeon Richter, AbbVie, sepranolone (UC1010) / Asarina Pharma
Review, Journal: Recent advances in understanding/management of premenstrual dysphoric disorder/premenstrual syndrome. (Pubmed Central) - May 17, 2022
If confirmed, neuroinflammation could lead both to develop targeted anti-inflammatory therapies and to define prevention strategies for the associated chronic inflammatory risk in PMS/PMDD. Finally, the observed association between premenstrual disorders and psychological diseases may guide prompt and adequate interventions to achieve a better quality of life.
- |||||||||| golexanolone (GR3027) / Karolinska Development, sepranolone (UC1010) / Asarina Pharma
Clinical, Review, Journal: Positive GABA receptor modulating steroids and their antagonists: Implications for clinical treatments. (Pubmed Central) - Apr 20, 2022
The progesterone metabolite allopregnanolone (Allo) is a positive GABA receptor modulating steroid with potent effects...We have demonstrated that isoallopregnanolone (Isoallo), the 3β-OH sibling of Allo, functions as a GABA receptor modulating steroid antagonist (GAMSA) but without any effects of its own on GABA receptors...In humans, vigilance, cognition and pathological electroencephalogram were improved in patients with hepatic encephalopathy on treatment with GR3027. In conclusion GAMSAs are a new possible treatment for disorders and symptoms caused by hyperactivity in the GABA system.
- |||||||||| sepranolone (UC1010) / Asarina Pharma
Journal: Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals. (Pubmed Central) - Dec 21, 2021
Moreover, an increase of dihydroprogesterone and isoallopregnanolone in the hippocampus, cerebellum, and cerebral cortex was also reported...In addition, an increase in dehydroepiandrosterone was associated with a decrease in testosterone levels in the hypothalamus of GF mice. Our findings suggest that the absence of microbes affects the neuroactive steroids in the periphery and the brain, supporting the evidence of a microbiota-mediated modulation of neuroendocrine pathways involved in preserving host brain functioning.
- |||||||||| sepranolone (UC1010) / Asarina Pharma
Journal: Neuroactive steroids and depression in early pregnancy. (Pubmed Central) - Oct 5, 2021
This work suggests a dynamic relationship between NAS and PND; whereas low ALLO levels have been previously associated with postpartum depression, earlier in pregnancy a higher metabolism of P4 to ALLO (and higher ALLO levels) is associated with depression. Some women may show a hormone-sensitive depressive response to acute increases in NAS metabolism in early pregnancy.
- |||||||||| sepranolone (UC1010) / Asarina Pharma
Preclinical, Journal: Isoallopregnanolone reduces tic-like behaviors in the D1CT-7 mouse model of Tourette syndrome. (Pubmed Central) - May 27, 2021
These effects were comparable to those elicited by both the benchmark TS therapy haloperidol (0.3 mg kg , i.p.), as well as finasteride (25 mg kg , i.p.)...Finally, isoAP opposed the enhancement of tic-like behaviors induced by AP (15 mg/kg, IP). Given that isoAP is well-tolerated and has an optimal safety profile, these data suggest that this steroid may have therapeutic properties in TS.
- |||||||||| sepranolone (UC1010) / Asarina Pharma
Enrollment closed, Trial completion date, Trial primary completion date: APH204: A Study Investigating the Efficacy and Safety of Sepranolone in Women With Menstrual Migraine (clinicaltrials.gov) - Oct 28, 2020
P2, N=84, Active, not recruiting,
Active, not recruiting --> Completed | N=225 --> 475 | Trial primary completion date: Apr 2020 --> Jul 2020 Recruiting --> Active, not recruiting | Trial completion date: Nov 2020 --> Mar 2021 | Trial primary completion date: Nov 2020 --> Mar 2021
- |||||||||| sepranolone (UC1010) / Asarina Pharma, allopregnanolone (LJPC-0712) / La Jolla Pharma
Review, Journal: Effects of GABA active steroids in the female brain with focus on the premenstrual dysphoric disorder. (Pubmed Central) - Oct 18, 2019
This was shown in a randomized, placebo-controlled clinical trial in which the primary outcome was change in symptom scoring on the DRSP (Daily Rating of Severity of Problems): the treatment reduced negative mood scores (p<0.005) as well as total DRSP scores (p<0.01) compared to placebo in women with PMDD. In conclusion, the underlying studies of this review provide evidence that allopregnanolone is the provoking factor behind the negative mood symptoms in PMDD and that isoallopregnanolone could ameliorate the symptoms due to its ability to antagonize the allopregnanolone effect on the GABAA receptor.
- |||||||||| sepranolone (UC1010) / Asarina Pharma
Enrollment closed, Trial completion date, Trial primary completion date: A Study of Efficacy and Safety of Sepranolone (UC1010) in Patients With Premenstrual Dysphoric Disorder (PMDD) (clinicaltrials.gov) - Sep 23, 2019
P2, N=225, Active, not recruiting,
In conclusion, the underlying studies of this review provide evidence that allopregnanolone is the provoking factor behind the negative mood symptoms in PMDD and that isoallopregnanolone could ameliorate the symptoms due to its ability to antagonize the allopregnanolone effect on the GABAA receptor. Recruiting --> Active, not recruiting | Trial completion date: Feb 2020 --> May 2020 | Trial primary completion date: Nov 2019 --> Feb 2020
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