ATOSIBAN

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C43H67N11O12S2
Molecular Weight	994.1924
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 2849		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 8583	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
The oxytocin receptor system: structure, function, and regulation.	2001 Apr	11274341
Tocolysis with beta-adrenergic receptor agonists.	2001 Aug	11561912
Effectiveness and safety of the oxytocin antagonist atosiban versus beta-adrenergic agonists in the treatment of preterm labour. The Worldwide Atosiban versus Beta-agonists Study Group.	2001 Feb	11236112
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
Design of oxytocin antagonists, which are more selective than atosiban.	2001 Sep	11587184
Spontaneous contractions of myometrium from humans, non-human primate and rodents are sensitive to selective oxytocin receptor antagonism in vitro.	2001 Sep	11563467
NO-induced relaxation of labouring and non-labouring human myometrium is not mediated by cyclic GMP.	2001 Sep	11522613
Involvement of oxytocin and vasopressin in the pathophysiology of preterm labor and primary dysmenorrhea.	2002	12436949
Effects of mating stimuli and oxytocin on plasma cortisol concentration in gilts.	2002 Mar	14666160
Involvement of cholecystokinin receptor in the inhibition of gastric emptying by oxytocin in male rats.	2002 Nov	12457239
Oxytocin antagonists for tocolysis in preterm labour -- a systematic review.	2002 Nov	12444392
Exploring the role of Tractocile in everyday clinical practice.	2003 Apr	12763126
Effects of alpha- and beta-adrenergic receptor stimulation and oxytocin receptor blockade on milking characteristics in dairy cows before and after removal of the teat sphincter.	2003 Aug	12916823
An update on the controversies of tocolytic therapy for the prevention of preterm birth.	2003 Jan	12580832
Effectiveness and safety of the oxytocin antagonist atosiban versus beta-adrenergic agonists in the treatment of preterm labour.	2003 Jan	12504956
Evidence that oxytocin is a physiological component of LH regulation in non-pregnant women.	2003 Jul	12832367
The oxytocin receptor.	2003 Jul	12826328
Oxytocin and fetal membranes in preterm labor: current concepts and clinical implication.	2003 Jun	12857435
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
Involvement of oxytocin in spinal antinociception in rats with inflammation.	2003 Sep 5	12914962
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
Centrally administered oxytocin elicits exaggerated grooming in oxytocin null mice.	2004 Jun	15219775
Delaying preterm delivery at the threshold of viability.	2004 Jun	15203596
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
Recent pharmacological advances in the treatment of preterm membrane rupture, labour and delivery.	2004 Sep	15330729
[Tocolysis by first intention with atosiban].	2005 Apr	15894214
[Licensed or non-licensed tocolysis?].	2005 Apr	15894213
Acute tocolysis.	2005 Apr	15758607
The oxytocin receptor antagonist atosiban inhibits cell growth via a "biased agonist" mechanism.	2005 Apr 22	15705593
Oxytocin mediates the estrogen-dependent contractile activity of endothelin-1 in human and rabbit epididymis.	2005 Aug	15860558
Visual compatibility of atosiban acetate with four drugs.	2005 Dec 1	16303899
[Pharmacoeconomic assessment of two tocolysis protocols for the inhibition of premature delivery].	2005 Jan-Feb	15773798
Oxytocin receptor antagonists for inhibiting preterm labour.	2005 Jul 20	16034931
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
Pharmacokinetic interaction studies of atosiban with labetalol or betamethasone in healthy female volunteers.	2005 Nov	16225568
Does insulin release kinins in rats?	2005 Nov 21	16297383
2,5-diketopiperazines as potent, selective, and orally bioavailable oxytocin antagonists. 2. Synthesis, chirality, and pharmacokinetics.	2005 Nov 3	16250654
Atosiban and nifedipin for the treatment of preterm labor.	2005 Oct	16043178
Design of peptide oxytocin antagonists with strikingly higher affinities and selectivities for the human oxytocin receptor than atosiban.	2005 Oct	15880385
Possible neural mediation of the central effects of oxytocin on uterine motility.	2005 Sep	16105822
Synthesis of oxytocin analogues with replacement of sulfur by carbon gives potent antagonists with increased stability.	2005 Sep 30	16277299
Oxytocin stimulates secretory processes in lactating rabbit mammary epithelial cells.	2006 Jan 1	16166151
The extracorporeal perfusion of the swine uterus as an experimental model: The effect of tocolytic drugs.	2006 May 1	16202502

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

ANTOCILE

Preferred 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

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