ATOSIBAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C43H67N11O12S2
Molecular Weight	994.189
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]1(NC(=O)[C@@]([H])(NC(=O)[C@@H](CC2=CC=C(OCC)C=C2)NC(=O)CCSSC[C@H](NC(=O)[C@H](CC(N)=O)NC1=O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCN)C(=O)NCC(N)=O)[C@@H](C)CC)[C@@H](C)O

InChI

InChIKey=VWXRQYYUEIYXCZ-OBIMUBPZSA-N

InChI=1S/C43H67N11O12S2/c1-5-23(3)35-41(63)53-36(24(4)55)42(64)50-29(20-32(45)56)38(60)51-30(43(65)54-17-8-10-31(54)40(62)49-27(9-7-16-44)37(59)47-21-33(46)57)22-68-67-18-15-34(58)48-28(39(61)52-35)19-25-11-13-26(14-12-25)66-6-2/h11-14,23-24,27-31,35-36,55H,5-10,15-22,44H2,1-4H3,(H2,45,56)(H2,46,57)(H,47,59)(H,48,58)(H,49,62)(H,50,64)(H,51,60)(H,52,61)(H,53,63)/t23-,24+,27-,28+,29-,30-,31-,35-,36-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.medicines.org.uk/emc/medicine/4297

Atosiban (brand name Tractocile) is a competitive antagonist of human oxytocin at receptor level. In rats and guinea pigs, atosiban was shown to bind to oxytocin receptors, to decrease the frequency of contractions and the tone of the uterine musculature, resulting in a suppression of uterine contractions. Atosiban was also shown to bind to the vasopressin receptor, thus inhibiting the effect of vasopressin. Tractocile is indicated to delay imminent pre-term birth in pregnant adult women with: − regular uterine contractions of at least 30 seconds duration at a rate of ≥ 4 per 30 minutes − a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of ≥ 50% − a gestational age from 24 until 33 completed weeks − a normal foetal heart rate. Atosiban does not have U.S. Food and Drug Administration (FDA) approval for use in the United States.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Oxytocin receptor 19 Target ID: CHEMBL2049 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16302826 \| https://www.ncbi.nlm.nih.gov/pubmed/7932368	Antagonist 2778		59.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Preterm birth 2 Sources: https://www.medicines.org.uk/emc/medicine/4297	Preventing		Approved 8429	Tractocile Approved Use Tractocile is indicated to delay imminent pre-term birth in pregnant adult women with: − regular uterine contractions of at least 30 seconds duration at a rate of ≥ 4 per 30 minutes − a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of ≥ 50% − a gestational age from 24 until 33 completed weeks − a normal foetal heart rate Launch Date 2000

PubMed

Title	Date	PubMed
Receptor binding of oxytocin and vasopressin antagonists and inhibitory effects on isolated myometrium from preterm and term pregnant women.	1999 Oct	10519430
Oxytocin antagonist disrupts hypotension-evoked renin secretion and other responses in conscious rats.	2001 Mar	11171655
[Tocolysis. Atosiban, an ocytcin-receptor antagonist].	2001 May	11397999
The oxytocin antagonist atosiban versus the beta-agonist terbutaline in the treatment of preterm labor. A randomized, double-blind, controlled study.	2001 May	11328217
Treatment of preterm labor with the oxytocin antagonist atosiban: a double-blind, randomized, controlled comparison with salbutamol.	2001 Oct	11574128
Oxytocin decreases carrageenan induced inflammation in rats.	2001 Sep	11514032
[Special management for threatened preterm delivery in multiple pregnancies].	2002 Nov	12454633
In vitro study of tocolytic effect of rofecoxib, a specific cyclo-oxygenase 2 inhibitor. Comparison and combination with other tocolytic agents.	2002 Sep	12269693
The in vitro effect of dual combinations of ritodrine, nicardipine and atosiban on contractility of pregnant rat myometrium.	2003 Aug	12892684
Pharmacology of (2S,4Z)-N-[(2S)-2-hydroxy-2-phenylethyl]-4-(methoxyimino) -1-[(2'-methyl[1,1'-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxamide, a new potent and selective nonpeptide antagonist of the oxytocin receptor.	2003 Jul	12660315
The effects of a progesterone metabolite, 5 beta-dihydroprogesterone, on oxytocin receptor binding in human myometrial membranes.	2003 Jun	12798477
Review of clinical experience with atosiban and the Tractocile Efficacy Assessment Survey in Europe (TREASURE) study protocol.	2003 Mar	12661796
Significant delay of birth in advanced preterm labour at 23 gestational weeks with an oxytocin antagonist.	2003 May 1	12694983
Atosiban treatment for uterine hyperactivity during active labor: a pilot study.	2004	15085889
Emerging issues over the choice of nifedipine, beta-agonists and atosiban for tocolysis in spontaneous preterm labour--a proposed systematic review by the International Preterm Labour Council.	2004 Apr	15203610
Management options for preterm labour in Canada.	2004 Apr	15115623
Current medical therapy in the prevention and treatment of preterm labour.	2004 Dec	15691786
Tocolysis and preterm labour.	2004 Dec	15534440
Preterm birth.	2004 Jun	15652088
Evaluation of the maternal and neonatal effects of the oxytocin antagonist, atosiban, in a cross-fostering study in rats.	2004 Nov	15336713
Inhibitory effect of barusiban and atosiban on oxytocin-induced contractions of myometrium from preterm and term pregnant women.	2004 Sep	15350251
The Gordian knot of developing tocolytics.	2004 Sep	15350245
Recent pharmacological advances in the treatment of preterm membrane rupture, labour and delivery.	2004 Sep	15330729
Acute tocolysis.	2005 Apr	15758607
Barusiban, a new highly potent and long-acting oxytocin antagonist: pharmacokinetic and pharmacodynamic comparison with atosiban in a cynomolgus monkey model of preterm labor.	2005 Apr	15671092
The oxytocin receptor antagonist atosiban inhibits cell growth via a "biased agonist" mechanism.	2005 Apr 22	15705593
Inhibition of trigemino-hypoglossal reflex in rats by oxytocin is mediated by mu and kappa opioid receptors.	2005 Feb 21	15713278
Ontogenesis and functional aspects of oxytocin and vasopressin gene expression in the thymus network.	2005 Jan	15589039
Oxytocin microinjected into dorsal motor nucleus of the vagus excites gallbladder motility via NMDA receptor-NO-cGMP pathway.	2005 Jan 25	15680949
[Pharmacoeconomic assessment of two tocolysis protocols for the inhibition of premature delivery].	2005 Jan-Feb	15773798
Tocolysis with atosiban: experience in the management of premature labor before 24 weeks of pregnancy.	2005 Jun	15909190
Tocolytic therapy and clinical experience. Combination therapy.	2005 Mar	15715603
Adverse effects of tocolytic therapy.	2005 Mar	15715600
Possible neural mediation of the central effects of oxytocin on uterine motility.	2005 Sep	16105822

Patents

Sample Use Guides

In Vivo Use Guide

Tractocile (Atosiban) is administered intravenously in three successive stages: an initial bolus dose (6.75 mg), performed with Tractocile 6.75 mg/0.9 ml solution for injection, immediately followed by a continuous high dose infusion (loading infusion 300 micrograms/min) of Tractocile 37.5 mg/5 ml concentrate for solution for infusion during three hours, followed by a lower dose of Tractocile 37.5 mg/5 ml concentrate for solution for infusion (subsequent infusion 100 micrograms/min) up to 45 hours. The duration of the treatment should not exceed 48 hours. The total dose given during a full course of Tractocile therapy should preferably not exceed 330.75 mg of atosiban. Intravenous therapy using the initial bolus injection should be started as soon as possible after diagnosis of pre-term labour. Once the bolus has been injected, proceed with the infusion (See Summary of Product Characteristics of Tractocile 37.5 mg/5 ml, concentrate for solution for infusion). In the case of persistence of uterine contractions during treatment with Tractocile, alternative therapy should be considered.

Route of Administration: Intravenous

In Vitro Use Guide

Atosiban had significant inhibitory effects on myometrial contractions of myometrial strips from healthy pregnant women at concentrations as low as 1 ug/mL.

Name

Type

Language

ATOSIBAN

Official Name

English

ATOSIBAN [MI]

Common Name

English

ORF 22164

Code

English

CAP-476

Code

English

atosiban [INN]

Common Name

English

ATOSIBAN [USAN]

Common Name

English

ORF-22164

Code

English

RW-22164

Code

English

ANTOCILE

Brand Name

English

F-314

Code

English

ATOSIBAN [MART.]

Common Name

English

RWJ-22164

Code

English

TRACTOCILE

Brand Name

English

1-(3-MERCAPTOPROPIONIC ACID)-2-(3-(P-ETHOXYPHENYL)-D-ALANINE)-4-L-THREONINE-8-L-ORNITHINEOXYTOCIN

Common Name

English

ANTOCIN II

Brand Name

English

ANTOCIN

Brand Name

English

GLYCINAMIDE, O-ETHYL-N-(3-MERCAPTO-1-OXOPROPYL)-D-TYROSYL-L-ISOLEUCYL-L-THREONYL-L-ASPARAGINYL-L-CYSTEINYL-L-PROLYL-L-ORNITHYL-, CYCLIC (1->5)-DISULFIDE

Systematic Name

English

OXYTOCIN, 1-(3-MERCAPTOPROPANOIC ACID)-2-(O-ETHYL-D-TYROSINE)-4-L-THREONINE-8-L-ORNITHINE-

Common Name

English

Atosiban [WHO-DD]

Common Name

English

RWJ 22164

Code

English

CAP-581

Code

English

TRACTOCIL

Brand Name

English

CAP-449

Code

English

Classification Tree Code System Code

WHO-VATC

QG02CX01