β-adrenoceptor ( Ki = 7.1 nM )

Oxprenolol is lipophilic[3]. The permeability rate constant of oxiprenolol across human abdominal skin is 1.54 ± 1.54×10-3 cm/h [3].

Peak plasma drug levels within the normal therapeutic range are produced along with effective beta-blockade when oxiprenolol (200 mg/kg/day; po; daily for 3 weeks) is administered[2].

Binding characteristics of the beta-blockers and beta-agonists with the beta-adrenoceptors were investigated in 3H-dihydroalprenolol (3H-DHA) binding to rat heart membranes treated with neuraminidase. When 60% of the total sialic acid content in the membranes was removed, reproducibility of the binding assay became much better than was attainable without neuraminidase treatment, and the maximum density of beta-adrenoceptors was increased. These data suggest that the binding of the test compounds with the beta-adrenergic receptors in cardiac muscle was under the influence of the sialic acid of the glycocalyx of the membrane. The 3H-DHA binding sites in membranes treated with neuraminidase showed a strict stereo-specificity when tested with propranolol. The ranking order of inhibition of beta-antagonists or agonists is: dl-propranolol > Oxprenolol > than alprenolol > pindolol > YM-09538 > labetalol > acebutolol > atenolol > metoprolol > sotalol > butoxamine > practolol as antagonists or l-isoproterenol > l-epinephrine > l-norepinephrine as agonists. A good correlation (r = 0.91, P less than 0.001) was observed between the Ki values observed by the present binding assay and the pA2 observed in the guinea-pig atria relative to the positive inotropic effect by Bieth et al. (Br. J. Pharmacol. 68, 563-569, 1980), indicating that the present method will be useful for screening new beta-adrenergic receptor antagonists or agonists. [1]

Animal/Disease Models: Male rats (230 to 300 g body wt) of the Wistar strain[2]
Doses: 200 mg/kg
Route of Administration: Administered po (oral gavage) daily for 3 weeks
Experimental Results: This dosage produced effective beta-blockade.

Absorption, Distribution and Excretion
Oral bioavailability is 20-70%. Metabolism/Metabolites Hepatic metabolism. Known human metabolites of oxyprolol include oxyprolol glucuronide. Biological Half-Life 1-2 hours

4631 Human TDLo oral 50 mg/kg Heart: pulse rate; Heart: other changes; Lung, pleural or respiratory: other changes, British Medical Journal, 1(776), 1977
4631 Mouse oral LD50 375 mg/kg, US Patent Document #5326774
4631 Mouse intraperitoneal LD50 170 mg/kg Lung, pleural or respiratory: dyspnea, Polish Journal of Pharmacology and Pharmaceutical Sciences, 25(145), 1973
4631 Mouse intravenous LD50 20 mg/kg, US Patent Document #5326774

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71172 Female oral LDLo 90 mg/kg Behavior: general anesthesia; Heart: arrhythmia (including conduction changes); Lung, pleural or respiratory: cyanosis, British Medical Journal, 1(552), 1977
71172 rat oral LD50 214 mg/kg, Drug Research, 35(1236), 1985 [PMID:2866775]
71172 rat intraperitoneal LD50 147 mg/kg Behavior: somnolence (overall activity inhibition), Clinical Reports, 7(3131), 1973
71172 rat subcutaneous LD50 940 mg/kg Behavior: seizures or effects on epileptic threshold; Behavior: ataxia; Lung, pleural or respiratory: dyspnea Arzneimittel-Forschung. Drug Research, 18(164), 1968 [PMID:5695373]
71172 rat intravenous LD50 33 mg/kg Behavioral: seizures or effects on the epileptic threshold; Behavioral: ataxia; Lung, pleural, or respiratory: dyspnea. Arzneimittel-Forschung. Drug Research., 18(164), 1968 [PMID:5695373]

[1]. Binding Characteristics of 3H-dihydroalprenolol to Beta-Adrenoceptors of Rat Heart Treated With Neuraminidase. Jpn J Pharmacol. 1983 Aug;33(4):851-7.

[2]. Abrupt Withdrawal of Chronic Beta-Blockade: Adaptive Changes in Cyclic AMP and Contractility. J Mol Cell Cardiol. 1981 Nov;13(11):999-1009.

[3]. A comparative in vitro study of percutaneous penetration of β-blockers in human skin. International journal of pharmaceutics, 2000, 194(2): 249-259.

1-(propyl-2-ylamino)-3-(2-prop-2-enoxyphenoxy)-2-propanol is an aromatic ether.
A β-adrenergic antagonist used to treat hypertension, angina pectoris, arrhythmias, and anxiety.
Oxyprolol is a lipophilic, non-selective β-adrenergic receptor antagonist with antiarrhythmic, antianginal, and antihypertensive effects. Oxyprolol competitively binds to and blocks the action of β1-adrenergic receptors in the heart, thereby reducing myocardial contractility and heart rate. This leads to a decrease in cardiac output and a reduction in blood pressure. Furthermore, oxyprolol inhibits the release of renin, a hormone secreted by the kidneys that causes vasoconstriction.
A β-adrenergic antagonist used to treat hypertension, angina pectoris, arrhythmias, and anxiety.
Drug Indications
For the treatment of hypertension, angina pectoris, arrhythmias, and anxiety.

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Mechanism of Action
Like other β-adrenergic antagonists, oprophal competitively binds to sympathetic receptors with adrenergic neurotransmitters such as catecholamines. Similar to propranolol and timolol, oprophal binds to β1-adrenergic receptors in cardiac and vascular smooth muscle, inhibiting the effects of catecholamines such as adrenaline and noradrenaline, thereby reducing heart rate, cardiac output, and systolic and diastolic blood pressure. It also blocks β2-adrenergic receptors in bronchiolar smooth muscle, causing vasoconstriction. Oprophal inhibits renin production by binding to β2-receptors in the juxtaglomerular apparatus, thereby inhibiting the production of angiotensin II and aldosterone. Therefore, oprophal inhibits vasoconstriction and water retention induced by angiotensin II and aldosterone, respectively.

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Pharmacodynamics
Oprol is a non-selective beta-blocker with intrinsic sympathomimetic activity.Oprol is a lipophilic molecule, thus it can cross the blood-brain barrier. Therefore, compared to hydrophilic ligands such as atenolol, sotalol, and nadolol, it is more likely to cause central nervous system-related side effects. Oprol is a potent beta-blocker and should not be used in patients with asthma because it may cause irreversible airway failure and inflammation. Oprol is a lipophilic, non-selective beta-adrenergic receptor antagonist with antiarrhythmic, antianginal, and antihypertensive effects. Oprol competitively binds to and blocks the function of β1-adrenergic receptors in the heart, thereby reducing myocardial contractility and heart rate. This leads to decreased cardiac output and lower blood pressure. Furthermore, oprol inhibits the release of renin, a hormone secreted by the kidneys that causes vasoconstriction.
It is a β-adrenergic antagonist used to treat hypertension, angina, arrhythmia and anxiety.

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In this study, as a continuation of a previous study (which reported on two β-blockers, celilol and bisoprolol (Modamio et al., 1998)), we compared the in vitro transdermal permeation properties of propranolol, oproprol, metoprolol and atenolol (including celilol and bisoprolol) and assessed the potential efficacy of each drug. In addition, correlations were established among the physicochemical parameters of the selected β-blockers, particularly lipophilicity expressed as an intrinsic partition coefficient, to determine whether optimal permeability could be achieved, thereby determining the predictive potential of these physicochemical parameters. [3]

C15H23NO3

265.34802

265.168

C, 67.90; H, 8.74; N, 5.28; O, 18.09

6452-71-7

Oxprenolol hydrochloride;6452-73-9;Oxprenolol-d7;1189805-10-4

4631

Typically exists as solid at room temperature

1.0479 (rough estimate)

408.57°C (rough estimate)

78-80°

1.5000 (estimate)

2.38

2

4

9

19

246

0

C=CCOC1=CC=CC=C1OCC(CNC(C)C)O

CEMAWMOMDPGJMB-UHFFFAOYSA-N

InChI=1S/C15H23NO3/c1-4-9-18-14-7-5-6-8-15(14)19-11-13(17)10-16-12(2)3/h4-8,12-13,16-17H,1,9-11H2,2-3H3

1-(propan-2-ylamino)-3-(2-prop-2-enoxyphenoxy)propan-2-ol

oxprenolol; 6452-71-7; dl-Oxprenolol; Coretal; (+-)-Oxprenolol; Osprenololo [DCIT]; Oxprenololum; Oxprenololum [INN-Latin];

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.)