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| Formula | C40H63N9O8S |
| Molar mass | 830.06 g·mol−1 |
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Barusiban (INN) (code name FE-200440) is a non-peptide drug which is among the most potent and selective oxytocin receptor antagonists known. [1] [2] It was trialed by Ferring Pharmaceuticals as a treatment of preterm labor but failed to demonstrate effectiveness and was not pursued any further. [1] [3]
Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Present in animals since early stages of evolution, in humans it plays roles in behavior that include social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin is released into the bloodstream as a hormone in response to sexual activity and during labour. It is also available in pharmaceutical form. In either form, oxytocin stimulates uterine contractions to speed up the process of childbirth. In its natural form, it also plays a role in maternal bonding and milk production. Production and secretion of oxytocin is controlled by a positive feedback mechanism, where its initial release stimulates production and release of further oxytocin. For example, when oxytocin is released during a contraction of the uterus at the start of childbirth, this stimulates production and release of more oxytocin and an increase in the intensity and frequency of contractions. This process compounds in intensity and frequency and continues until the triggering activity ceases. A similar process takes place during lactation and during sexual activity.
Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible for the development of female secondary sexual characteristics such as the breasts, widening of the hips and a female-associated pattern of fat distribution. It is also important in the development and maintenance of female reproductive tissues such as the mammary glands, uterus and vagina during puberty, adulthood and pregnancy. It also has important effects in many other tissues including bone, fat, skin, liver, and the brain.
Uterine contractions are muscle contractions of the uterine smooth muscle that occur during the menstrual cycle and labour. Uterine contractions occur throughout the menstrual cycle in the non-pregnant state and throughout gestation.
Desipramine, sold under the brand name Norpramin among others, is a tricyclic antidepressant (TCA) used in the treatment of depression. It acts as a relatively selective norepinephrine reuptake inhibitor, though it does also have other activities such as weak serotonin reuptake inhibitory, α1-blocking, antihistamine, and anticholinergic effects. The drug is not considered a first-line treatment for depression since the introduction of selective serotonin reuptake inhibitor (SSRI) antidepressants, which have fewer side effects and are safer in overdose.
Ergometrine, also known as ergonovine and sold under the brand names Ergotrate, Ergostat, and Syntometrine among others, is a medication used to cause contractions of the uterus to treat heavy vaginal bleeding after childbirth. It can be used either by mouth, by injection into a muscle, or injection into a vein. It begins working within 15 minutes when taken by mouth and is faster in onset when used by injection. Effects last between 45 and 180 minutes.
A contraction stress test (CST) is performed near the end of pregnancy to determine how well the fetus will cope with the contractions of childbirth. The aim is to induce contractions and monitor the fetus to check for heart rate abnormalities using a cardiotocograph. A CST is one type of antenatal fetal surveillance technique.
Biological half-life is the time taken for concentration of a biological substance to decrease from its maximum concentration (Cmax) to half of Cmax in the blood plasma. It is denoted by the abbreviation .
Vasopressin receptor 1A (V1AR), or arginine vasopressin receptor 1A is one of the three major receptor types for vasopressin, and is present throughout the brain, as well as in the periphery in the liver, kidney, and vasculature.
The oxytocin receptor, also known as OXTR, is a protein which functions as receptor for the hormone and neurotransmitter oxytocin. In humans, the oxytocin receptor is encoded by the OXTR gene which has been localized to human chromosome 3p25.
Carbetocin, sold under the brand names Pabal among others, is a medication used to prevent excessive bleeding after childbirth, particularly following Cesarean section. It appears to work as well as oxytocin. Due to it being less economical than other options, use is not recommended by NHS Scotland. It is given by injection into a vein or muscle.
Demoxytocin (INN), also known as desaminooxytocin or deaminooxytocin, as well as 1-(3-mercaptopropanoic acid)oxytocin ([Mpa1]OT), is an oxytocic peptide drug that is used to induce labor, promote lactation, and to prevent and treat puerperal (postpartum) mastitis. Demoxytocin is a synthetic analogue of oxytocin and has similar activities, but is more potent and has a longer half-life in comparison. Unlike oxytocin, which is given via intravenous injection, demoxytocin is administered as a buccal tablet formulation.
Neuromedin S is a 36-amino acid neuropeptide found in the brain of humans and other mammals. It is produced in the suprachiasmatic nucleus of the hypothalamus and is related to neuromedin U. It is thought to be involved in regulation of circadian rhythm and also has appetite suppressant effects, as well as regulating the release of several other peptide hormones including vasopressin, luteinizing hormone, and oxytocin.
WAY-267464 is a potent, selective, non-peptide agonist for the oxytocin receptor, with negligible affinity for the vasopressin receptors. Contradictorily however, though originally described as selective for the oxytocin receptor and lacking affinity for the vasopressin receptors, it has since been reported to also act as a potent vasopressin V1A receptor antagonist. WAY-267464 has been shown to cross the blood–brain barrier to a significantly greater extent than exogenously applied oxytocin, and in animal tests produces centrally-mediated oxytocinergic actions such as anxiolytic effects, but with no antidepressant effect evident. It was developed by a team at Ferring Pharmaceuticals. WAY-267464 was under investigation for the potential clinical treatment of anxiety disorders by Wyeth, and reached the preclinical stage of development, but no development has been reported as of 2011.
Epelsiban is an orally bioavailable drug which acts as a selective and potent oxytocin receptor antagonist. It was initially developed by GlaxoSmithKline (GSK) for the treatment of premature ejaculation in men and then as an agent to enhance embryo or blastocyst implantation in women undergoing embryo or blastocyst transfer associated with in vitro fertilization (IVF)., and was also investigated for use in the treatment of adenomyosis.
Retosiban also known as GSK-221,149-A is an oral drug which acts as an oxytocin receptor antagonist. It is being developed by GlaxoSmithKline for the treatment of preterm labour. Retosiban has high affinity for the oxytocin receptor and has greater than 1400-fold selectivity over the related vasopressin receptors
5β-Dihydroprogesterone is an endogenous neurosteroid and an intermediate in the biosynthesis of pregnanolone and epipregnanolone from progesterone. It is synthesized from progesterone by the enzyme 5β-reductase.
Amastatin, also known as 3-amino-2-hydroxy-5-methylhexanoyl-L-valyl-L-valyl-L-aspartic acid, is a naturally occurring, competitive and reversible aminopeptidase inhibitor that was isolated from Streptomyces sp. ME 98-M3. It specifically inhibits leucyl aminopeptidase, alanyl aminopeptidase, bacterial leucyl aminopeptidase, leucyl/cystinyl aminopeptidase (oxytocinase/vasopressinase), and, to a lesser extent, glutamyl aminopeptidase, as well as other aminopeptidases. It does not inhibit arginyl aminopeptidase. Amastatin has been found to potentiate the central nervous system effects of oxytocin and vasopressin in vivo. It also inhibits the degradation of met-enkephalin, dynorphin A, and other endogenous peptides.
Diarylpropionitrile (DPN), also known as 2,3-bis(p-hydroxyphenyl)propionitrile (2,3-BHPPN), is a synthetic, nonsteroidal, and highly selective agonist of ERβ (IC50 = 15 nM) that is used widely in scientific research to study the function of this receptor. It is 70-fold more selective for ERβ over ERα, and has 100-fold lower affinity for GPER (GPR30) relative to estradiol. DPN produces antidepressant- and anxiolytic-like effects in animals via activation of the endogenous oxytocin system. First reported in 2001, DPN was the first selective ERβ agonist to be discovered, and was followed by prinaberel (ERB-041, WAY-202041), WAY-200070, and 8β-VE2 in 2004, ERB-196 (WAY-202196) in 2005, and certain phytoestrogens like liquiritigenin and nyasol (cis-hinokiresinol) since 2007.
Levonorgestrel butanoate (LNG-B), or levonorgestrel 17β-butanoate, is a steroidal progestin of the 19-nortestosterone group which was developed by the World Health Organization (WHO) in collaboration with the Contraceptive Development Branch (CDB) of the National Institute of Child Health and Human Development as a long-acting injectable contraceptive. It is the C17β butanoate ester of levonorgestrel, and acts as a prodrug of levonorgestrel in the body. The drug is at or beyond the phase III stage of clinical development, but has not been marketed at this time. It was first described in the literature, by the WHO, in 1983, and has been under investigation for potential clinical use since then.
Synthetic oxytocin, sold under the brand name Pitocin among others, is a medication made from the peptide oxytocin. As a medication, it is used to cause contraction of the uterus to start labor, increase the speed of labor, and to stop bleeding following delivery. For this purpose, it is given by injection either into a muscle or into a vein.
