β adrenergic receptor
Metipranolol binds to β-adrenergic receptors with high affinity, functioning as a non-selective antagonist of the β-adrenoceptor. It binds to primary rabbit iris and ciliary body homogenates with a Ki of 34 nM. In functional assays, metipranolol inhibits relaxation induced by isoproterenol in guinea pig atrium and by fenoterol in rat uterus, with pA₂ values of 8.3 and 8.4, respectively. In addition to its β-blocking activity, metipranolol also inhibits iron/ascorbate-induced lipid peroxidation with an IC₅₀ of 6.9 µM and sodium nitroprusside-induced lipid peroxidation with an IC₅₀ of 25.1 µM, exhibiting antioxidant properties. The compound has weak local anaesthetic and myocardial depressant activity. Metipranolol is a potent non-selective beta blocker that breaks down quickly to produce desacetylmetipranolol, its active metabolite. Owing to its well-characterized β-blocking activity, metipranolol hydrochloride is commonly used in research related to cardiovascular pharmacology and ophthalmology.

Metipranolol is applied topically to treat glaucoma and systemically to treat arterial hypertension[1].
In vitro, metipranolol demonstrates significant activity at β-adrenergic receptors and exhibits antioxidant properties. The compound inhibits iron/ascorbate-induced lipid peroxidation with an IC₅₀ of 6.9 µM and sodium nitroprusside-induced lipid peroxidation with an IC₅₀ of 25.1 µM. In functional assays using isolated tissues, metipranolol inhibits isoproterenol-induced relaxation in guinea pig atrium (pA₂ = 8.3) and fenoterol-induced relaxation in rat uterus (pA₂ = 8.4). In primary retinal cell cultures, metipranolol (100 μM) inhibits anoxia-induced cell death, suggesting a potential neuroprotective effect. The compound's antioxidant properties may contribute to its protective effects in ocular tissues. Metipranolol's ability to inhibit lipid peroxidation suggests that it may reduce oxidative stress in various tissues. The compound's effects on β-adrenergic receptors can be studied in cells expressing these receptors, with readouts including cAMP accumulation and downstream signaling.

In vivo, metipranolol demonstrates efficacy in reducing intraocular pressure and managing hypertension. When administered topically in the eye, metipranolol reduces elevated as well as normal intraocular pressure, whether or not accompanied by glaucoma. The reduction in intraocular pressure appears to be via decreased production of aqueous humour. In animal models, topical ocular application of 0.3% metipranolol decreases α-chymotrypsin-induced intraocular pressure elevation in rabbits. Systemically, metipranolol has been used in the treatment of arterial hypertension. The compound is pharmacologically active in reducing sympathetic nervous system–mediated cardiovascular effects. Metipranolol is administered as 0.1% or 0.3% ophthalmic drops, with one drop instilled twice daily into the affected eye. If intraocular pressure is not at a satisfactory level on this regimen, use of more frequent administration or a larger dose is not known to be of benefit.

In vitro receptor binding assays for metipranolol typically employ radioligand displacement techniques using membrane preparations from tissues or cells expressing β-adrenergic receptors. For β₁ and β₂ receptor binding, membranes from tissues such as rabbit iris and ciliary body, guinea pig atrium, or rat uterus are commonly used. The assay involves incubating metipranolol at varying concentrations with the membrane preparation and a fixed concentration of a radiolabeled β-adrenergic receptor antagonist, such as [³H]-CGP-12177 or [¹²⁵I]-iodocyanopindolol. Following incubation, bound and free radioligand are separated by rapid filtration through glass fiber filters, and the radioactivity retained on the filters is measured. Non-specific binding is determined in the presence of a high concentration of an unlabeled β-blocker such as propranolol. Binding affinity (Ki) values are calculated from competition curves using nonlinear regression analysis. For functional assays, isolated tissue preparations such as guinea pig atrium or rat uterus are used to measure inhibition of agonist-induced responses.

In vitro cellular assays for metipranolol typically employ cell lines or primary cells that express β-adrenergic receptors. Cells such as cardiomyocytes, vascular smooth muscle cells, or retinal cells are cultured in appropriate media and treated with metipranolol at various concentrations. For studies evaluating antioxidant activity, cells are exposed to oxidative stress-inducing agents such as iron/ascorbate or sodium nitroprusside in the presence or absence of metipranolol, and lipid peroxidation is measured using assays such as thiobarbituric acid reactive substances (TBARS). For studies investigating β-adrenergic receptor antagonism, cells are stimulated with isoproterenol or other β-agonists in the presence or absence of metipranolol, and downstream signaling such as cAMP accumulation is measured. In primary retinal cells, metipranolol (100 μM) inhibits anoxia-induced cell death, and cell viability is assessed using standard assays such as MTT or LDH release.

In vivo animal experiments for metipranolol typically employ rabbit or rodent models to evaluate its effects on intraocular pressure and cardiovascular function. For ocular studies, rabbits are administered metipranolol topically as ophthalmic drops at concentrations of 0.1% or 0.3%, and intraocular pressure is measured using tonometry before and after treatment. Elevated intraocular pressure is induced by α-chymotrypsin injection or other methods, and the reduction in IOP following metipranolol treatment is assessed. For cardiovascular studies, rats or other rodents are administered metipranolol orally or intravenously, and blood pressure and heart rate are measured using tail-cuff plethysmography or telemetry. The compound's effects on sympathetic nervous system activity are evaluated by measuring responses to β-adrenergic agonists or by assessing cardiovascular parameters at baseline. Dosing regimens vary depending on the experimental objectives, with acute studies using single doses and chronic studies using repeated daily administration.

The pharmacokinetic properties of metipranolol are characterized by rapid absorption and metabolism following topical or systemic administration. When applied topically in the eye, metipranolol is absorbed through the cornea and reaches the intraocular tissues, where it exerts its effects on aqueous humour production. The compound breaks down quickly to produce desacetylmetipranolol, its active metabolite. Metipranolol has a molecular weight of 345.86 and a molecular formula of C₁₇H₂₇NO₄·HCl. Following systemic administration, the compound is distributed throughout the body and undergoes hepatic metabolism. The pharmacokinetics of metipranolol are consistent with its use as a once- or twice-daily medication for hypertension and glaucoma. The compound's rapid metabolism to an active metabolite may contribute to its duration of action. As with other β-blockers, the pharmacokinetics of metipranolol may be influenced by factors such as age, hepatic function, and concomitant medications.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Based on its physicochemical properties and ocular route of administration, metenolol eye drops are not expected to have any adverse effects on breastfed infants. Some guidelines indicate that the gel formulation is preferred over the solution formulation. To significantly reduce the amount of medication that enters breast milk after instillation, press your finger against the tear duct near the corner of your eye for at least 1 minute, then blot away any excess medication with absorbent paper. ◉ Effects on Breastfed Infants
As of the revision date, no published information was found regarding metenolol. A study of breastfeeding mothers taking beta-blockers found a numerically increased number of adverse events, but this was not statistically significant. Although the infants' ages were matched to those in the control group, the ages of the affected infants were not specified. None of the mothers were taking metenolol.
◉ Effects on Lactation and Breast Milk
As of the revision date, no published information was found regarding the effects of beta-blockers or metenolol during normal lactation. A study of six patients with hyperprolactinemia and galactorrhea found no change in serum prolactin levels after beta-adrenergic blockade with propranolol.
The toxicity profile of metipranolol is consistent with that of non-selective β-adrenergic receptor antagonists. Common adverse effects associated with ophthalmic use include ocular burning, stinging, and irritation. Systemic absorption of topically applied metipranolol can lead to cardiovascular effects, including bradycardia, hypotension, and heart block, particularly in patients with preexisting cardiac conditions. The compound has weak local anaesthetic and myocardial depressant activity. As with other β-blockers, metipranolol should be used with caution in patients with asthma, chronic obstructive pulmonary disease, or other conditions that may be exacerbated by β-blockade. The compound may mask the symptoms of hypoglycemia in diabetic patients. Contraindications include sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure. The safety of metipranolol in pregnancy and lactation has not been established, and its use should be guided by clinical judgment.

[1]. Acute effect of metipranolol on the retinal circulation. Br J Ophthalmol. 1998 Aug;82(8):892-6.

Metipranolol hydrochloride is a non-selective β-adrenergic receptor antagonist used systemically for arterial hypertension and topically for glaucoma management. It is formulated as ophthalmic drops in 0.1% and 0.3% solutions, with the usual adult dose being one drop in the affected eye(s) twice daily. Ophthalmic metipranolol is used to treat glaucoma, a condition in which increased pressure in the eye can lead to gradual loss of vision. It controls glaucoma but does not cure it. Generic OptiPranolol eye drops are available in one strength--metipranolol 0.3 percent solution. Metipranolol binds to primary rabbit iris and ciliary body homogenates (Ki = 34 nM) and inhibits relaxation induced by isoproterenol in guinea pig atrium and by fenoterol in rat uterus (pA₂s = 8.3 and 8.4, respectively). It also inhibits iron/ascorbate and sodium nitroprusside-induced lipid peroxidation with IC₅₀ values of 6.9 µM and 25.1 µM, respectively. The compound has weak local anaesthetic and myocardial depressant activity and breaks down quickly to produce desacetylmetipranolol.

C17H28CLNO4

345.86152

345.171

C, 59.04; H, 8.16; Cl, 10.25; N, 4.05; O, 18.50

36592-77-5

656682

Solid powder

484.5ºC at 760 mmHg

246.8ºC

3.467

3

5

8

23

348

0

CC1=C(OC(C)=O)C(C)=C(C)C(OCC(O)CNC(C)C)=C1.[H]Cl

BLWNYSZZZWQCKO-UHFFFAOYSA-N

InChI=1S/C17H27NO4.ClH/c1-10(2)18-8-15(20)9-21-16-7-11(3)17(22-14(6)19)13(5)12(16)4;/h7,10,15,18,20H,8-9H2,1-6H3;1H

[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]-2,3,6-trimethylphenyl] acetate;hydrochloride

Metipranolol hydrochloride; OptiPranolol; Metipranolol; Metipranolol HCl

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)

DMSO: ~100 mg/mL (~289.1 mM)
H2O: ≥ 100 mg/mL (~289.1 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.23 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 25.0 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.23 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 25.0 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.23 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (289.13 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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