β1-receptor
Prenalterol targets the β1-adrenergic receptor, a G protein-coupled receptor predominantly found in the heart. By binding to and activating this receptor, Prenalterol stimulates adenylyl cyclase, increasing the production of cyclic AMP (cAMP). This leads to the activation of protein kinase A (PKA), which phosphorylates various proteins involved in cardiac excitation-contraction coupling. The result is an increase in intracellular calcium, leading to enhanced myocardial contractility (positive inotropic effect) and increased heart rate (positive chronotropic effect). Its selectivity for β1 over β2 receptors is a key feature.

In vitro, Prenalterol is characterized by its selective agonism of the β1-adrenergic receptor. Its activity is typically studied using radioligand binding assays to determine its affinity for β1 and β2 receptors. Functional assays, such as measuring the stimulation of cAMP production in cells expressing the receptors, confirm its agonist activity. While specific EC50 or Ki values are not provided in the search results, its classification as a selective β1 agonist indicates a higher affinity for β1 over β2 receptors.

Gastrointestinal motility is influenced by adrenergic modulation. Our aim was to identify specific subtypes of adrenergic receptors involved in inhibitory mechanisms that modulate gut smooth muscle contractile activity. Muscle strips of rat ileal longitudinal muscle were evaluated for spontaneous contractile activity and for equimolar dose-responses (10(-7) to 3 x 10(-5) M) to the adrenergic agents norepinephrine (nonselective agonist), phenylephrine (alpha(1)-agonist), clonidine (alpha(2)-agonist), prenalterol (beta(1)-agonist), ritodrine (beta(2)-agonist), and ZD7114 (beta(3)-agonist) in the presence and absence of tetrodotoxin (nonselective nerve blocker). Norepinephrine (3 x 10(-5) M) inhibited 65 +/- 6% (mean +/- SEM) of spontaneous contractile activity. The same molar dose of ritodrine, phenylephrine, or ZD7114 resulted in less inhibition (46 +/- 7%, 31 +/- 5%, and 39 +/- 3%, respectively; P < 0.05). The calculated molar concentration of ZD7114 needed to induce 50% inhibition was similar to that of norepinephrine, whereas higher concentrations of phenylephrine or ritodrine were required. Clonidine and prenalterol had no effect on contractile activity. Blockade of intramural neural transmission by tetrodotoxin affected the responses to ritodrine and phenylephrine (but not to norepinephrine or ZD7114), suggesting that these agents exert part of their effects via neurally mediated enteric pathways. Our results suggest that adrenergic modulation of contractile activity in the rat ileum is mediated primarily by muscular beta(3)-, beta(2)-, and alpha(1)-receptor mechanisms; the latter two also involve neural pathways [1].

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In vivo, Prenalterol exerts positive inotropic and chronotropic effects, increasing cardiac output. It has been studied for its potential use in managing heart failure. Although specific pharmacokinetic parameters like half-life or bioavailability are not detailed in the search results, its effects are consistent with beta-1 adrenergic stimulation. In animal models, it would be expected to increase left ventricular contractility and stroke volume. Its selectivity for β1 receptors would result in fewer bronchial and peripheral vascular side effects compared to non-selective beta agonists.

In vitro receptor binding assays are performed using membrane preparations from cells or tissues expressing β1 and β2 adrenergic receptors. The membranes are incubated with a radiolabeled antagonist, such as [¹²⁵I]iodocyanopindolol, and varying concentrations of Prenalterol. After incubation, the samples are filtered, and the bound radioactivity is counted. The Ki values for both receptor subtypes are determined from the competition curves to assess the compound's selectivity.

For in vitro cell-based functional assays, cells expressing the human β1-adrenergic receptor are used. Cells are pre-incubated with various concentrations of Prenalterol, and the production of cAMP is measured using a cAMP ELISA or HTRF assay. The EC50, representing the concentration needed to achieve half-maximal stimulation, is calculated from the dose-response curve. A parallel assay using cells expressing the β2 receptor is performed to confirm selectivity.

In vivo animal studies are conducted in rodent models of heart failure, such as the rat model of myocardial infarction. Prenalterol is administered via intravenous injection or oral gavage, and cardiac function is assessed using echocardiography or invasive hemodynamic measurements (e.g., left ventricular pressure). The increase in ejection fraction and cardiac output is measured. For pharmacokinetic studies, blood samples are collected at various time points to measure plasma drug concentrations using LC-MS/MS.

[1]. alpha- and beta-adrenergic receptor mechanisms in spontaneous contractile activity of rat ileal longitudinal smooth muscle. J Gastrointest Surg. 2005;9(2):227-235.

C12H19NO3

225.28416

225.136

C, 63.98; H, 8.50; N, 6.22; O, 21.30

62340-37-8

61260-05-7 (HCl);62340-37-8;

182336

White to off-white solid powder

1.118g/cm3

397.7ºC at 760mmHg

194.3ºC

1.52

3

4

6

16

179

0

CC(C)NCC(COC1=CC=C(C=C1)O)O

ADUKCCWBEDSMEB-UHFFFAOYSA-N

InChI=1S/C12H19NO3/c1-9(2)13-7-11(15)8-16-12-5-3-10(14)4-6-12/h3-6,9,11,13-15H,7-8H2,1-2H3

4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenol

Prenalterol; 57526-81-5; Prenalterolum; (S)-4-(2-Hydroxy-3-(isopropylamino)propoxy)phenol; Prenalterol [INN:BAN]; Prenalterolum [INN-Latin]; 4-[(2S)-2-hydroxy-3-(propan-2-ylamino)propoxy]phenol; EINECS 260-791-5;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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