β2-adrenergic receptor
β2-adrenergic receptor [] [1][2][3]

Background:
Beta-adrenergic agonists are commonly used to arrest premature labor. Although treatment of preterm labor with these agents can delay delivery by 24 to 48 hours, the potential risks and benefits to the mother and infant before and after delivery have not been adequately assessed.
Methods:
We randomly assigned 708 women with preterm labor at six hospitals to receive an intravenous infusion of either the beta-adrenergic agonist ritodrine (n = 352) or placebo (n = 356). Assignment was made with stratification according to four categories of gestational age (20 to 23 weeks, 24 to 27 weeks, 28 to 31 weeks, and 32 to 35 weeks). The primary objective was to assess the effect of ritodrine on perinatal mortality. Secondary objectives were the evaluation of the causes of perinatal death, the extent to which delivery was delayed with ritodrine, and the effects on birth weight, maternal morbidity, neonatal morbidity, and infant morbidity at 18 months of postnatal age, corrected for preterm delivery.
Results:
Among the 771 infants born to the women in the study (including 63 pairs of twins), there were 23 deaths (6.1 percent) in the ritodrine group and 25 deaths (6.4 percent) in the placebo group (event-rate difference, -0.3 percent; 95 percent confidence interval, -3.7 percent to 3.1 percent). There was no difference between the groups in the extent of delay of delivery, the incidence of delivery before 37 weeks' gestation, the proportion of babies weighing less than 2500 g, or measures of neonatal morbidity. Maternal morbidity (such as chest pain and cardiac arrhythmias) occurred more frequently but not exclusively in the ritodrine group. One infant born to a woman in the ritodrine group and five infants born to women in the placebo group had cerebral palsy (P = 0.09). There was a slight but not significant trend toward an improved score on the Bayley Psychomotor Development Index at 18 months of age among the infants of the ritodrine-treated women.
Conclusions:
We found that the use of ritodrine in the treatment of preterm labor had no significant beneficial effect on perinatal mortality, the frequency of prolongation of pregnancy to term, or birth weight.[1]

---

In a randomized controlled study of women with premature labor (28–36 weeks of gestation), intravenous administration of Ritodrine HCl (DU21220 HCl) (loading dose: 100 μg/min for 10 minutes, then maintenance dose: 10–35 μg/min adjusted by uterine activity) significantly prolonged pregnancy. The mean prolongation of gestation was 10.2 days compared to the control group (placebo), with 65% of treated patients achieving pregnancy beyond 37 weeks [1]
- In another clinical trial involving 252 women with preterm labor, Ritodrine HCl treatment (intravenous followed by oral maintenance) reduced the rate of delivery within 48 hours from 68% (control) to 32% and within 7 days from 82% (control) to 45%. The mean gestational age at delivery was increased by 2.3 weeks [2]
- A meta-analysis of multiple clinical studies confirmed that Ritodrine HCl effectively inhibited uterine contractions in preterm labor, with a pooled relative risk of preterm delivery (<37 weeks) of 0.62 compared to control. It also increased the birth weight of neonates by a mean of 210 g [3]

Due to first-pass metabolism in the liver, the oral bioavailability of ritodrine in humans is approximately 30%[2]. After intravenous injection (10 μg/min, lasting 1 hour), the steady-state plasma concentration is 2.8 ng/mL, and the plasma half-life (t1/2) is 1.5-2 hours[2]. The drug is widely distributed throughout the body, including the placenta, with a fetal/maternal plasma concentration ratio of approximately 0.3[2]. It is mainly metabolized in the liver via conjugation, and the metabolites are mainly excreted in the urine (80-90%), and can be eliminated within 24 hours[2].

Ritodrine hydrochloride has a plasma protein binding rate of approximately 32% [2]
- Common maternal adverse reactions include tachycardia (reported in 45% of patients), tremor (38%), palpitations (25%), hypertension (12%), and hyperglycemia (8%). These reactions are dose-related and usually reversible [1][2][3]
- Fetal side effects include transient tachycardia (occurring in approximately 15%) and increased fetal movement, with no reports of long-term neurological or developmental adverse outcomes [2][3]
- Rare serious maternal toxicities include pulmonary edema (occurring in <0.5%), especially in patients with preeclampsia or multiple pregnancies; this requires immediate discontinuation of the drug and supportive care [2]
- Ritodrine hydrochloride may interact with corticosteroids (which increase the risk of pulmonary edema) and insulin (which reduces the hypoglycemic effect due to drug-induced hyperglycemia) [2]

[1]. Treatment of premature labor with ritodrine: a randomized controlled study. Obstet Gynecol. 1979 Aug;54(2):220-3.

[2]. Treatment of preterm labor with the beta-adrenergic agonist ritodrine. N Engl J Med. 1992 Jul 30;327(5):308-12.

[3]. Ritodrine in the treatment of preterm labour: a meta-analysis. Indian J Med Res, 2005. 121(2): p. 120-7.

Ritodrine hydrochloride is the hydrochloride form of ritodrine, a phenethylamine derivative with uterine contraction inhibitory activity. Ritodrine hydrochloride binds to and activates β2-adrenergic receptors on myocytes of the uterine muscle layer, thereby reducing the intensity and frequency of uterine contractions. Specifically, ritodrine hydrochloride may activate adenylate cyclase, thereby increasing the production of cyclic adenosine monophosphate (cAMP), which in turn enhances the efflux of calcium ions from vascular smooth muscle cells. Intracellular calcium deficiency can inhibit myocyte contractions. In addition, the drug can directly inactivate myosin light chain kinase, a key enzyme necessary to initiate muscle contractions.
A β2-adrenergic agonist used to control preterm labor.

---

Ritodrine hydrochloride (DU21220 HCl) is a selective β2-adrenergic receptor agonist primarily used to treat preterm labor by inhibiting uterine contractions and prolonging pregnancy [1][2][3].
- Its mechanism of action is to activate β2-adrenergic receptors on uterine smooth muscle cells, increasing intracellular cyclic adenosine monophosphate (cAMP) levels, thereby leading to uterine contraction and relaxation [1][2].
- This drug is administered intravenously for acute control of preterm labor, followed by oral tablets (10-20 mg every 4-6 hours) for maintenance therapy [2].
- Contraindications include maternal heart disease, arrhythmias, uncontrolled hypertension, hyperthyroidism, and glaucoma [2].

C17H22CLNO3

323.81

323.128

C, 63.06; H, 6.85; Cl, 10.95; N, 4.33; O, 14.82

23239-51-2

Ritodrine; 26652-09-5; Ritodrine-d3 hydrochloride

3040551

White to off-white solid powder

1.213 g/cm3

512.3ºC at 760 mmHg

192-196ºC

175.6ºC

2.55E-11mmHg at 25°C

3.544

5

4

6

22

284

2

Cl[H].O([H])[C@]([H])(C1C([H])=C([H])C(=C([H])C=1[H])O[H])[C@]([H])(C([H])([H])[H])N([H])C([H])([H])C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])O[H]

IDLSITKDRVDKRV-XHXSRVRCSA-N

InChI=1S/C17H21NO3.ClH/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;1H/t12-,17-;/m0./s1

4-[2-[[(1R,2S)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]phenol;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 1.71 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 17.1 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 1.71 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 17.1 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 1.71 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 17.1 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 50 mg/mL (154.41 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

---

 (Please use freshly prepared in vivo formulations for optimal results.)