Clinical evaluation of the NK3 receptor antagonist fezolinetant (a.k.a. ESN364) for the treatment of menopausal hot flashes

Maturitas ◽  
2017 ◽  
Vol 103 ◽  
pp. 89-90 ◽  
Author(s):  
Herman Depypere ◽  
Dirk Timmerman ◽  
Gilbert Donders ◽  
Peter Sieprath ◽  
Steven Ramael ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Clinical Evaluation ◽  
Hot Flashes ◽  
Nk3 Receptor

scholarly journals SUN-LB58 Repeated Once-Daily Administration of the Non-Hormonal Neurokinin 1,3 Receptor Antagonist NT-814 Reduces LH, Estradiol and Progesterone in Healthy Women

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Waljit Singh Dhillo ◽  
Elizabeth Ballantyne ◽  
Kirsteen Donaldson ◽  
Mary Kerr ◽  
Mike Trower ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Hot Flashes ◽  
Uterine Fibroids ◽  
Daily Administration ◽  
Controlled Study ◽  
Once Daily ◽  
Healthy Women ◽  
Serum Lh ◽  
Gnrh Release ◽  
Nk3 Receptor

Abstract Introduction: Uterine fibroids (UF) affect up to 25% of women and endometriosis (EM) 10% of women worldwide. An ideal therapy would lower estradiol concentrations to reduce hormonal drive to the endometrium and myometrium, but not to the levels which cause the hot flashes and bone loss associated with current treatments. A target estradiol range of 110-180 pmol/L has been proposed1. GnRH secretion is modulated by neurokinin B (NKB) acting at the NK3 receptor via hypothalamic neurons expressing kisspeptin, NKB & dynorphin (KNDy neurons). In addition, Substance P acting at the NK1 receptor may also stimulate reproductive hormone release. We hypothesised that NT-814, a dual NK1,3 receptor antagonist, would reduce GnRH release and hence LH, estradiol and progesterone levels in women. This preliminary clinical study in healthy pre-menopausal women evaluated this hypothesis. Methods: We undertook a randomized, single-blind, placebo-controlled study. 32 healthy women attended for 2 consecutive menstrual cycles. In each cycle blood samples were taken on days 3/4, 9/10, 15/16 and 21/22 to measure serum sex hormone concentrations. No treatment was given in cycle 1 (baseline). During cycle 2, participants received placebo or one of three doses of NT-814 once per day; 40mg, 80mg or 120mg (n=8 per group) for up to 21 days. Results: Compared to placebo, NT-814 reduced LH, estradiol and progesterone concentrations in a dose-related manner. The median changes in average LH (IU/L) during cycle 2 compared to cycle 1 were: placebo, 0.16; 40mg, -0.13; 80mg, -0.46; 120mg, -0.58. Median change in average estradiol (pmol/L) in cycle 2 was: placebo, -16.5; 40mg, -9.3; 80mg, -92.1; 120mg, -141.4. The median changes in progesterone (nmol/L) on day 21/22 in cycle 2 compared to cycle 1 were: placebo, 3.2; 40mg, 8.0; 80mg, -5.7; 120mg, -19.4. The reductions in estradiol and progesterone with 120 mg NT-814 were significant (p=0.038 & p=0.046, respectively). There were no clear changes in FSH concentrations. Of note, in women treated with 120mg NT-814, the average estradiol level reduced from 310.8 pmol/L in cycle 1 to 179.8 pmol/L in cycle 2. Cycle length was extended by at least 6 days in 5 of 8 women receiving the 120 mg dose. NT-814 was well tolerated; no participant experienced hot flashes during treatment. Conclusions: Once-daily administration of the non-hormonal NK1,3 receptor antagonist NT-814 reduced serum LH, estradiol and progesterone in healthy women in a dose-related manner without causing vasomotor symptoms. The 120 mg dose of NT-814 lowered estradiol levels to potentially ideal levels for UF and EM treatment. These preliminary data support further studies with NT-814 to establish its efficacy and safety in treating patients with these hormone driven disorders. References: 1Barbieri RL Am J Obstet Gynaecol 1992 166 740-5.

scholarly journals Pharmacological activities of R-113281, a novel NK1, NK2 and NK3 receptor antagonist in vivo.

2000 ◽  
Vol 82 ◽  
pp. 111
Author(s):  
Yumiko Satoh ◽  
Emi Nosaka ◽  
Kazuhiro Ito ◽  
Takahide Nishi ◽  
Takeshi Yamaguchi
Keyword(s):  
Receptor Antagonist ◽  
Pharmacological Activities ◽  
Nk3 Receptor

Inhibition of inflammatory cell recruitment by the tachykinin NK3-receptor antagonist, SR 142801, in a murine model of asthma

2001 ◽  
Vol 421 (3) ◽  
pp. 201-205 ◽  
Author(s):  
Soazig Nénan ◽  
Noëlla Germain ◽  
Vincent Lagente ◽  
Xavier Emonds-Alt ◽  
Charles Advenier ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Murine Model ◽  
Inflammatory Cell ◽  
Cell Recruitment ◽  
Nk3 Receptor ◽  
Inflammatory Cell Recruitment

The development of a high affinity NK3 receptor antagonist

Peptides 1994 ◽  
1995 ◽  
pp. 712-713
Author(s):  
J. Eden ◽  
J. Hodgson ◽  
D. C. Horwell ◽  
W. Howson ◽  
M. C. Pritchard ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
High Affinity ◽  
Nk3 Receptor

Fezolinetant. Tachykinin NK3 receptor antagonist, Treatment of menopausal-related vasomotor symptoms

2020 ◽  
Vol 45 (8) ◽  
pp. 537
Author(s):  
G. D'Alessando ◽  
F. Barra ◽  
G. Evangelisti ◽  
S. Ferrero
Keyword(s):  
Receptor Antagonist ◽  
Vasomotor Symptoms ◽  
Nk3 Receptor
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