Chemical compound
Pharmaceutical compound
Ritodrine Pronunciation RY -toh-dreen Trade names Pre-Par, Utopar, Yutopar Other names DU-21220; 4-Hydroxy-β-hydroxy-N -(4-hydroxyphenylethyl)amphetamine; N -(4-Hydroxyphenylethyl)-4-hydroxynorephedrine AHFS /Drugs.com Micromedex Detailed Consumer Information Routes of By mouth , parenteral ATC code Legal status Protein binding ~56% Metabolism Hepatic , metabolites are inactive[ 1] Elimination half-life 1.7–2.6 hours
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 InfoCard 100.043.512 Formula C 17 H 21 N O 3 Molar mass −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
Y Key:IOVGROKTTNBUGK-SJCJKPOMSA-N
Y (verify)
Ritodrine , formerly sold under the brand name Yutopar among others, is a tocolytic drug used to stop premature labor .[ 2] [ 3] 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
Ritodrine 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 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 -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 .[ 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 INN Tooltip International Nonproprietary Name , USAN Tooltip United States Adopted Name , BAN Tooltip British Approved Name , and DCF Tooltip Dénomination Commune Française .[ 15] [ 16] hydrochloride salt , its generic name is ritodrine hydrochloride and this is its USAN Tooltip United States Adopted Name and BANM Tooltip British Approved Name .[ 15] [ 16] DU-21220 .[ 15] Pre-Par , Utopar , and Yutopar , among others.[ 15] [ 16]
See also
References
^ Finkelstein BW (1981). "Ritodrine (Yutopar, Merrell Dow Pharmaceuticals Inc.)". Drug Intelligence & Clinical Pharmacy . 15 (6): 425– 33. doi :10.1177/106002808101500601 . S2CID 75942075 . ^ 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 . ^ 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 . ^ 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 . ^ a b Kleemann A, Kutscher B (2022). Ullmann's Pharmaceuticals ISBN 978-3-527-80733-8 . Retrieved 30 August 2024 . ^ 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 . ^ 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 . ^ 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 . ^ 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 . ^ 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 . ^ Medicinal Chemistry of Adrenergics and Cholinergics Archived 2010-11-04 at the Wayback Machine ^ a b "Ritodrine" . PubChem . Retrieved 30 August 2024 .^ a b "C17H21NO3" . ChemSpider . 2024-08-30. Retrieved 2024-08-30 .^ a b "Ritodrine: Uses, Interactions, Mechanism of Action" . DrugBank Online . 31 December 1984. Retrieved 30 August 2024 .^ a b c d Schweizerischer Apotheker-Verein (2000). Index Nominum 2000: International Drug Directory ISBN 978-3-88763-075-1 . Retrieved 30 August 2024 . ^ a b c Morton IK, Hall JM (1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms ISBN 978-0-7514-0499-9 . Retrieved 30 August 2024 .
α1
Agonists Antagonists
Abanoquil Ajmalicine Alfuzosin Anisodamine Anisodine Atiprosin Atypical antipsychotics (e.g., brexpiprazole , clozapine , olanzapine , quetiapine , risperidone )Benoxathian Beta blockers (e.g., adimolol , amosulalol , arotinolol , carvedilol , eugenodilol , labetalol )Buflomedil Bunazosin Corynanthine Dapiprazole Domesticine Doxazosin Ergolines (e.g., acetergamine , ergotamine , dihydroergotamine , lisuride , nicergoline , terguride )Etoperidone Fenspiride Hydroxyzine Indoramin Ketanserin L-765,314 mCPP Mepiprazole Metazosin Monatepil Moxisylyte Naftopidil Nantenine Neldazosin Niaprazine Niguldipine Pardoprunox Pelanserin Perlapine Phendioxan Phenoxybenzamine Phentolamine Phenylpiperazine antidepressants (e.g., hydroxynefazodone , nefazodone , trazodone , triazoledione )Piperoxan Prazosin Quinazosin Quinidine Silodosin Spegatrine Spiperone Talipexole Tamsulosin Terazosin Tiodazosin Tolazoline Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin )Tricyclic antidepressants (e.g., amitriptyline , clomipramine , doxepin , imipramine , trimipramine )Trimazosin Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine )Urapidil WB-4101 Zolertine
α2
Agonists Antagonists
1-PP Adimolol Amesergide Aptazapine Atipamezole Atypical antipsychotics (e.g., asenapine , brexpiprazole , clozapine , lurasidone , olanzapine , paliperidone , quetiapine , risperidone , zotepine )Azapirones (e.g., buspirone , gepirone , ipsapirone , tandospirone )BRL-44408 Buflomedil Cirazoline Efaroxan Esmirtazapine Fenmetozole Fluparoxan Idazoxan Ketanserin Lisuride mCPP Mianserin Mirtazapine NAN-190 Pardoprunox Phentolamine Phenoxybenzamine Piperoxan Piribedil Rauwolscine Rotigotine Setiptiline Spegatrine Spiroxatrine Sunepitron Terguride Tolazoline Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine )Yohimbine
β
Phenethylamines Amphetamines Phentermines Cathinones Phenylisobutylamines (and further-extended) Catecholamines (and close relatives) Cyclized
Phenylalkylpyrrolidines 2-Benzylpiperidines (phenidates ) Phenylmorpholines (phenmetrazines) Phenyloxazolamines (aminorexes) Isoquinolines andtetrahydroisoquinolines 2-Aminoindanes 2-Aminotetralins Others / unsorted
1-Aminomethylindanes (e.g., 2CB-Ind , AMMI , bromojimscaline , jimscaline )2-ADN 2-Benzhydrylpyrrolidine 2C-B-5-hemiFLY-α6 (BNAP) 2C-B-PYR 2CBecca 2CJP 2CLisaB 2CLisaH 3-Benzhydrylmorpholine 3-Phenylpiperidines (e.g., 3-phenylpiperidine , 3-PPP , OSU-6162 (PNU-96391) , LPH-5 , LPH-48 , Z3517967757 (Z7757) )6-AB AL-1095 Aminochromes (e.g., adrenochrome , adrenolutin )Benzazepines (e.g., fenoldopam , lorcaserin , SCHEMBL5334361 )Benzocyclobutenes (e.g., 2CBCB-NBOMe , bromotomscaline , S33005 , TCB-2 , tomscaline )Benzoxepins (e.g., BBOX , IBOX , TFMBOX )Butyltolylquinuclidine Camfetamine Cypenamine (trans -2-phenylcyclopentylamine) Diphenidine Diphenylprolinol DMBMPP Ergolines (e.g., LSD )Fencamfamin GYKI-52895 HDMP-29 Ivabradine Methoxphenidine Methylmorphenate Milnacipran MT-45 2-Naphthylamine Org 6582 Partial ergolines (e.g., NDTDI , RU-27849 , DEIMDHPCA , DEMPDHPCA , DEMPDHPCA-2C-D , RU-27251 )PF-592,379 Phenylcyclopropylamines (e.g., DMCPA , TMT , tranylcypromine )Phenylpiracetams (e.g., phenylpiracetam , MRZ-9547 , RGPU-95 )Pyridopyrroloquinoxalines (e.g., lumateperone , deulumateperone , IHCH-7079 , IHCH-7086 , IHCH-7113 , ITI-1549 )Tetrahydrobenzopyranylamines (e.g., CT-5126 )Tolazoline Tricyclics (e.g., AMDA , AMDH , benzoctamine , dizocilpine , SpAMDA )ZC-B
Related compounds
2-Furylethylamine 2-Pyrrolylethylamine 3-Pyrrolylethylamine 3-Pyrrolylpropylamine 2-Tetrahydrofurylethylamine 4-Benzylpiperidine 7-AB Alkylamines (e.g., 1,3-DMBA Tooltip 1,3-dimethylbutylamine , 1,4-DMAA Tooltip 1,4-dimethylamylamine , heptaminol , iproheptine , isometheptene , methylhexanamine/1,3-DMAA , octodrine , oenethyl , tuaminoheptane )Benzylamines (e.g., benzylamine , α-methylbenzylamine , MDM1EA , ALPHA , M-ALPHA , pargyline )Benzylpiperazines (e.g., benzylpiperazine , MDBZP , fipexide )Cyclohexylaminopropanes (e.g., propylhexedrine , norpropylhexedrine )Cyclopentylaminopropanes (e.g., isocyclamine , cyclopentamine )Phenoxyethylamines (e.g., 3,4,5-trimethoxyphenoxyethylamine , CT-4719 , ORG-37684 )Phenylalkenylamines (e.g., phenylbutenamine )Phenylalkynylamines (e.g., phenylbutynamine )Phenylpiperazines (e.g., 1-phenylpiperazine , mCPP Tooltip meta-chlorophenylpiperazine , TFMPP Tooltip trifluoromethylphenylpiperazine , oMPP Tooltip ortho-methylphenylpiperazine , pFPP Tooltip para-fluorophenylpiperazine , pMeOPP Tooltip para-methoxyphenylpiperazine )Phenylpropylamines (e.g., phenylpropylamine , homo-MDA , homo-MDMA )Thienylaminopropanes (thiopropamines) (e.g., thiopropamine , methiopropamine , thiothinone )
