Ritodrine

{{Drugbox

| Watchedfields = changed

| verifiedrevid = 464382866

| image = Ritodrine.svg

| width = 250px

| image2 = Ritodrine ball-and-stick model.png

| width2 = 225px

| pronounce = {{IPAc-en|ˈ|r|aɪ|t|oʊ|d|r|iː|n}} {{respell|RY|toh|dreen}}

| tradename = Pre-Par, Utopar, Yutopar

| Drugs.com = {{drugs.com|CONS|ritodrine}}

| pregnancy_AU =

| pregnancy_US =

| legal_AU =

| legal_UK =

| legal_US_comment = Discontinued

| routes_of_administration = By mouth, parenteral

| bioavailability =

| protein_bound = ~56%

| metabolism = Hepatic, metabolites are inactive{{cite journal| vauthors = Finkelstein BW |title=Ritodrine (Yutopar, Merrell Dow Pharmaceuticals Inc.)|journal=Drug Intelligence & Clinical Pharmacy|date=1981|volume=15|issue=6 |pages=425–33|doi=10.1177/106002808101500601 |s2cid=75942075 }}

| metabolites =

| elimination_half-life = 1.7–2.6 hours

| excretion =

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 26652-09-5

| ATC_prefix = G02

| ATC_suffix = CA01

| PubChem = 33572

| IUPHAR_ligand = 7294

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00867

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 30971

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = I0Q6O6740J

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D02359

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 785

| synonyms = DU-21220; 4-Hydroxy-β-hydroxy-N-(4-hydroxyphenylethyl)amphetamine; N-(4-Hydroxyphenylethyl)-4-hydroxynorephedrine

| IUPAC_name = 4-{{Square bracket open}}2-{{Square bracket open|2}}(1R,2S)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl{{Square bracket close}}amino{{Square bracket close}}ethyl{{Square bracket close}}phenol

| C = 17

| H = 21

| N = 1

| O = 3

| SMILES = O[C@H](c1ccc(O)cc1)[C@@H](NCCc2ccc(O)cc2)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C17H21NO3/c1-12(17(21)14-4-8-16(20)9-5-14)18-11-10-13-2-6-15(19)7-3-13/h2-9,12,17-21H,10-11H2,1H3/t12-,17-/m0/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = IOVGROKTTNBUGK-SJCJKPOMSA-N

}}

Ritodrine, formerly sold under the brand name Yutopar among others, is a tocolytic drug used to stop premature labor.{{cite journal | vauthors = Yaju Y, Nakayama T | title = Effectiveness and safety of ritodrine hydrochloride for the treatment of preterm labour: a systematic review | journal = Pharmacoepidemiol Drug Saf | volume = 15 | issue = 11 | pages = 813–822 | date = November 2006 | pmid = 16981213 | doi = 10.1002/pds.1317 | url = }}{{cite journal |vauthors=Li X, Zhang Y, Shi Z |title=Ritodrine in the treatment of preterm labour: a meta-analysis |journal=The Indian Journal of Medical Research |volume=121 |issue=2 |pages=120–7 |date=February 2005 |pmid=15756046 |url=http://www.icmr.nic.in/ijmr/2005/February/0207.pdf |access-date=2008-10-05 |archive-date=2019-08-25 |archive-url=https://web.archive.org/web/20190825003349/https://www.icmr.nic.in/ijmr/2005/February/0207.pdf |url-status=dead }} It was withdrawn from the US market, according to the FDA Orange Book. It was available in oral tablets or as an injection and was typically used as the hydrochloride salt.

The drug acts as a selective β₂-adrenergic receptor agonist.{{cite journal | vauthors = Mangrella M, Torella M, Russo F, Rossi F, Piucci B, Cantoni V | title = [Pharmacology of ritodrine] | language = Italian | journal = Minerva Ginecol | volume = 51 | issue = 6 | pages = 233–244 | date = June 1999 | pmid = 10479875 | doi = | url = }}

It was first approved for medical use in the United States in 1984.

Medical uses

Ritodrine is used to treat preterm labor.

Contraindications

Possible contraindications of ritodrine include type 2 diabetes, high blood pressure, and migraines.

Side effects

Most side effects of β₂-adrenergic receptor agonists result from their concurrent β₁-adrenergic receptor agonistic activity, and include increase in heart rate, rise in systolic blood pressure, decrease in diastolic blood pressure, chest pain secondary to myocardial infarction, and arrhythmia. β-Adrenergic receptor agonists may also cause fluid retention secondary to decrease in water clearance, which when added to the tachycardia and increased myocardial work, may result in heart failure. In addition, they increase gluconeogenesis in the liver and muscle resulting in hyperglycemia, which increases insulin requirements in diabetic patients. The passage of β-adrenergic receptor agonists through the placenta does occur and may be responsible for fetal tachycardia, as well as hypoglycemia or hyperglycemia at birth. It has also been associated with postpartum bleeding.{{Citation needed|date=October 2010}}

Ritodrine has been reported rarely to cause serious side effects including rhabdomyolysis, hepatotoxicity, leukopenia, pulmonary edema, and psychiatric symptoms, among others.{{cite journal | vauthors = Sun L, Tang M, Peng M, Xu P, Wang Y | title = Ritodrine-induced rhabdomyolysis and psychiatric symptoms: a case report and literature review | journal = BMC Pregnancy Childbirth | volume = 23 | issue = 1 | pages = 11 | date = January 2023 | pmid = 36611175 | pmc = 9824990 | doi = 10.1186/s12884-022-05299-2 | doi-access = free | url = }}{{cite journal | vauthors = Ceriani R, Borroni G, Bissoli F | title = Ritodrine-related liver injury. Case reports and review of the literature | journal = Ital J Gastroenterol Hepatol | volume = 30 | issue = 3 | pages = 315–317 | date = June 1998 | pmid = 9759604 | doi = | url = }}{{cite journal | vauthors = Wu CD, Chao AS, Cheng PJ, Soong YK | title = Ritodrine-induced leukopenia: a case report and literature review | journal = Changgeng Yi Xue Za Zhi | volume = 19 | issue = 4 | pages = 388–391 | date = December 1996 | pmid = 9041773 | doi = | url = }}{{cite journal | vauthors = Castro Fernández M, Romero Gómez M, Grande Santamaría L, Caballero Manzano M | title = [Acute hepatitis due to ritodrine] | language = Spanish | journal = Med Clin (Barc) | volume = 113 | issue = 6 | pages = 239 | date = September 1999 | pmid = 10472614 | doi = | url = }}{{cite journal | vauthors = Alper M, Cohen WR | title = Pulmonary edema associated with ritodrine and dexamethasone treatment of threatened premature labor. A case report | journal = J Reprod Med | volume = 28 | issue = 5 | pages = 349–352 | date = May 1983 | pmid = 6152991 | doi = | url = }}

Pharmacology

=Pharmacodynamics=

Ritodrine is a short-acting β₂-adrenergic receptor agonist – a class of medication used for smooth muscle relaxation (other similar drugs are used in asthma or other pulmonary diseases such as salbutamol [albuterol]). Since ritodrine has a bulky N-substituent, it has high β₂-adrenergic receptor selectivity. Also, the 4-hydroxy group on the benzene ring is important for activity as it is needed to form hydrogen bonds. Since the drug is β₂-selective, it is used for premature labor.[http://pharmaxchange.info/notes/medicinal_chemistry/adrenergics_cholinergics.html Medicinal Chemistry of Adrenergics and Cholinergics] {{webarchive|url=https://web.archive.org/web/20101104022742/http://pharmaxchange.info/notes/medicinal_chemistry/adrenergics_cholinergics.html |date=2010-11-04 }}

=Pharmacokinetics=

The 4-hydroxy group of ritodrine makes it susceptible to metabolism by catechol-O-methyl transferase (COMT).

Chemistry

Ritodrine, also known as 4-hydroxy-β-hydroxy-N-(4-hydroxyphenylethyl)amphetamine or as N-(4-hydroxyphenylethyl)-4-hydroxynorephedrine, is a substituted phenethylamine and amphetamine derivative.{{cite web | title=Ritodrine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/33572 | access-date=30 August 2024}}{{cite web | title=C17H21NO3 | website=ChemSpider | date=2024-08-30 | url=https://www.chemspider.com/Chemical-Structure.30971.html | access-date=2024-08-30}}{{cite web | title=Ritodrine: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=31 December 1984 | url=https://go.drugbank.com/drugs/DB00867 | access-date=30 August 2024}}

The experimental log P of ritodrine is 2.4 and its predicted ranges from 1.53 to 2.3.

History

Ritodrine was first approved for medical use in the United States in 1984.{{cite book | vauthors = Kleemann A, Kutscher B | title=Ullmann's Pharmaceuticals | publisher=Wiley | year=2022 | isbn=978-3-527-80733-8 | url=https://books.google.com/books?id=94JlEAAAQBAJ&pg=RA4-PA9 | access-date=30 August 2024 | page=4-PA9}}

Society and culture

=Names=

Ritodrine is the generic name of the drug and its {{Abbrlink|INN|International Nonproprietary Name}}, {{Abbrlink|USAN|United States Adopted Name}}, {{Abbrlink|BAN|British Approved Name}}, and {{Abbrlink|DCF|Dénomination Commune Française}}.{{cite book | author=Schweizerischer Apotheker-Verein | title=Index Nominum 2000: International Drug Directory | publisher=Medpharm Scientific Publishers | year=2000 | isbn=978-3-88763-075-1 | url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA923 | access-date=30 August 2024 | page=923}}{{cite book | vauthors = Morton IK, Hall JM | title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms | publisher=Springer Netherlands | year=1999 | isbn=978-0-7514-0499-9 | url=https://books.google.com/books?id=mqaOMOtk61IC&pg=PA249 | access-date=30 August 2024 | page=249}} In the case of the hydrochloride salt, its generic name is ritodrine hydrochloride and this is its {{Abbrlink|USAN|United States Adopted Name}} and {{Abbrlink|BANM|British Approved Name}}. It is also known by its developmental code name DU-21220. The drug has been sold under brand names including Pre-Par, Utopar, and Yutopar, among others.