Fezolinetant

Fezolinetant is an antagonist of the neurokinin 3 receptor (NK3R), used for the treatment of menopausal hot flushes.

Signaling Pathways >> GPCR/G Protein >> Neurokinin Receptor

Signaling Pathways >> Neuronal Signaling >> Neurokinin Receptor

Research Areas >> Others

Fezolinetant (ESN364, 1 mg/kg, iv bolus) reversibly inhibits the regular, pulsatile secretion of LH in the ovarectomized ewe. ESN364 represses the pulse pattern of LH in all treated animals. ESN364 (5 mg/kg, p.o.) lowers plasma LH, but not FSH, in the castrated monkey. ESN364 (10, 25, 50 mg/kg, orally) also blocks the LH surge and decreases ovarian hormone levels throughout the menstrual cycle in monkeys[1].

On the day of the experiment, the NK3R antagonist ESN364 is formulated in physiological saline with 9% 2-hydroxypropyl-β-cyclodextrin at a concentration of 2 mg/mL. At 240 minutes after the initiation of blood sampling, ESN364 (1 mg/kg, n=5) or vehicle (n=5) is administered by an iv bolus injection at a dose volume of 0.5 mL/kg through the jugular cannulae, and the injected material is flushed into the animal with 5 mL of heparinized saline. Blood sampling resumes at the indicated intervals following this iv administration.

[1]. Fraser GL, et al. The NK3 Receptor Antagonist ESN364 Interrupts Pulsatile LH Secretion and Moderates Levels of Ovarian Hormones Throughout the Menstrual Cycle. Endocrinology. 2015 Nov;156(11):4214-25.

Substance P acetate salt | rolapitant | SB-222200 | Netupitant | [Sar9,Met(O2)11]-Substance P TFA | MLE-4901 | Succinyl-(Asp6,N-Me-Phe8)-Substance P (6-11) | Maropitant | NKP608 | Serlopitant | Talnetant | Y1 receptor antagonist 1 | [bAla8]-Neurokinin A(4-10) | Befetupitant