Ritodrine

Ritodrine
Clinical data
Pronunciation/ˈraɪtoʊdriːn/ RY-toh-dreen
Trade namesPre-Par, Utopar, Yutopar
Other namesDU-21220; 4-Hydroxy-β-hydroxy-N-(4-hydroxyphenylethyl)amphetamine; N-(4-Hydroxyphenylethyl)-4-hydroxynorephedrine
AHFS/Drugs.comMicromedex Detailed Consumer Information
Routes of
administration		Oral (tablets), parenteral (IV)
ATC code
Legal status
Legal status
  • US: Discontinued
Pharmacokinetic data
Protein binding~56%
MetabolismHepatic, metabolites are inactive[1]
Elimination half-life1.7–2.6 hours
Identifiers
  • 4-[2-[[(1R,2S)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]phenol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.043.512 Edit this at Wikidata
Chemical and physical data
FormulaC17H21NO3
Molar mass287.359 g·mol−1
3D model (JSmol)
  • O[C@H](c1ccc(O)cc1)[C@@H](NCCc2ccc(O)cc2)C
  • InChI=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 checkY
  • Key:IOVGROKTTNBUGK-SJCJKPOMSA-N checkY
  (verify)

Ritodrine, sold under the brand name Yutopar, is a tocolytic drug used to stop premature labor.[2][3] This drug has been removed from the US market, according to 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.[4]

It was first approved for medical use in the United States in 1984.[5]

Medical uses

Ridodrine is used to treat preterm labor.[2]

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[disambiguation needed] 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]

Ritodrine has been reported rarely to cause serious side effects including rhabdomyolysis, hepatotoxicity, leukopenia, pulmonary edema, and psychiatric symptoms, among others.[6][7][8][9][10]

Pharmacology

Pharmacodynamics

Ritodrine is a short-acting β2-adrenoreceptor 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.[11]

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.[12][13][14]

The experimental log P of ritodrine is 2.4 and its predicted ranges from 1.53 to 2.3.[12][13][14]

History

Ritodrine was first approved for medical use in the United States in 1984.[5]

Society and culture

Names

Ritodrine is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, BANTooltip British Approved Name, and DCFTooltip Dénomination Commune Française.[15][16] In the case of the hydrochloride salt, its generic name is ritodrine hydrochloride and this is its USANTooltip United States Adopted Name and BANMTooltip British Approved Name.[15][16] It is also known by its developmental code name DU-21220.[15] The drug has been sold under brand names including Pre-Par, Utopar, and Yutopar, among others.[15][16]

See also

References

  1. ^ Finkelstein BW (1981). "Ritodrine (Yutopar, Merrell Dow Pharmaceuticals Inc.)". Drug Intelligence & Clinical Pharmacy. 15 (6): 425–33. doi:10.1177/106002808101500601. S2CID 75942075.
  2. ^ a b Yaju Y, Nakayama T (November 2006). "Effectiveness and safety of ritodrine hydrochloride for the treatment of preterm labour: a systematic review". Pharmacoepidemiol Drug Saf. 15 (11): 813–822. doi:10.1002/pds.1317. PMID 16981213.
  3. ^ Li X, Zhang Y, Shi Z (February 2005). "Ritodrine in the treatment of preterm labour: a meta-analysis" (PDF). The Indian Journal of Medical Research. 121 (2): 120–7. PMID 15756046. Archived from the original (PDF) on 2019-08-25. Retrieved 2008-10-05.
  4. ^ Mangrella M, Torella M, Russo F, Rossi F, Piucci B, Cantoni V (June 1999). "[Pharmacology of ritodrine]". Minerva Ginecol (in Italian). 51 (6): 233–244. PMID 10479875.
  5. ^ a b Kleemann A, Kutscher B (2022). Ullmann's Pharmaceuticals. Wiley. p. 4-PA9. ISBN 978-3-527-80733-8. Retrieved 30 August 2024.
  6. ^ Sun L, Tang M, Peng M, Xu P, Wang Y (January 2023). "Ritodrine-induced rhabdomyolysis and psychiatric symptoms: a case report and literature review". BMC Pregnancy Childbirth. 23 (1): 11. doi:10.1186/s12884-022-05299-2. PMC 9824990. PMID 36611175.
  7. ^ Ceriani R, Borroni G, Bissoli F (June 1998). "Ritodrine-related liver injury. Case reports and review of the literature". Ital J Gastroenterol Hepatol. 30 (3): 315–317. PMID 9759604.
  8. ^ Wu CD, Chao AS, Cheng PJ, Soong YK (December 1996). "Ritodrine-induced leukopenia: a case report and literature review". Changgeng Yi Xue Za Zhi. 19 (4): 388–391. PMID 9041773.
  9. ^ Castro Fernández M, Romero Gómez M, Grande Santamaría L, Caballero Manzano M (September 1999). "[Acute hepatitis due to ritodrine]". Med Clin (Barc) (in Spanish). 113 (6): 239. PMID 10472614.
  10. ^ Alper M, Cohen WR (May 1983). "Pulmonary edema associated with ritodrine and dexamethasone treatment of threatened premature labor. A case report". J Reprod Med. 28 (5): 349–352. PMID 6152991.
  11. ^ Medicinal Chemistry of Adrenergics and Cholinergics Archived 2010-11-04 at the Wayback Machine
  12. ^ a b "Ritodrine". PubChem. Retrieved 30 August 2024.
  13. ^ a b "C17H21NO3". ChemSpider. 2024-08-30. Retrieved 2024-08-30.
  14. ^ a b "Ritodrine: Uses, Interactions, Mechanism of Action". DrugBank Online. 31 December 1984. Retrieved 30 August 2024.
  15. ^ a b c d Schweizerischer Apotheker-Verein (2000). Index Nominum 2000: International Drug Directory. Medpharm Scientific Publishers. p. 923. ISBN 978-3-88763-075-1. Retrieved 30 August 2024.
  16. ^ a b c Morton IK, Hall JM (1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Netherlands. p. 249. ISBN 978-0-7514-0499-9. Retrieved 30 August 2024.