β₁-adrenoceptor (β₁-AR)
It is a cardioselective β₁-receptor blocker with lipophilic properties and no intrinsic sympathomimetic activity (ISA). [1]

Naringin can inhibit the talinolol transport mediated by human OATP1A2-, rat Oatp1a5-, and rat Mdr1a in LLC-PK1 cells and the Xenopus laevis oocyte system, with IC50 values of 343, 12.7, and 604, respectively. μM[3].

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Talinolol was identified as a substrate for multiple drug transporters.
In LLC-PK1 cell monolayers, the secretory (basolateral-to-apical) permeability of talinolol was significantly higher than its absorptive (apical-to-basolateral) permeability in cells expressing human MDR1, rat Mdr1a, and rat Mdr1b. This directional transport was inhibited by cyclosporine A (10 µM), confirming that talinolol is a substrate for both human and rat P-gp.
In Xenopus laevis oocyte expression systems, talinolol uptake was significantly increased in oocytes expressing human OATP1A2, human OATP2B1, and rat Oatp1a5 compared to water-injected controls. The uptake was saturable with estimated kinetic parameters: for OATP1A2, Km = 714 ± 199 µM and Vmax = 105 ± 16 pmol/oocyte/120 min; for OATP2B1, Km = 629 ± 780 µM and Vmax = 138 ± 10 pmol/oocyte/120 min; for Oatp1a5, Km = 2000 ± 819 µM and Vmax = 59.9 ± 9.0 pmol/oocyte/60 min.
The inhibitory effect of naringin, a major component of grapefruit juice, on transporter-mediated talinolol transport was evaluated. Naringin inhibited human OATP1A2-mediated uptake with an IC50 of 343 ± 119 µM, and rat Oatp1a5-mediated uptake with an IC50 of 12.7 ± 3.1 µM. It had no inhibitory effect on human OATP2B1-mediated uptake up to 2000 µM. For P-gp, naringin did not inhibit human MDR1-mediated transport up to 2000 µM, but it did inhibit rat Mdr1a-mediated transport with an IC50 of 604 ± 169 µM. [3]

Talinol (20 mg/kg; i.p.) treatment raises hepatic AUC and plasma by 0–5 hours [2]. It is possible to increase the bioavailability of talinol and grapefruit juice (GFJ) in rats [3].

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Talinolol demonstrates various electrophysiological and therapeutic effects in patients.
Electrophysiological Effects in Healthy Subjects: After intravenous administration of 10-20 mg over 3-5 minutes, a slight depression in sinus node recovery time (SNRT, average prolongation of 164 ms) and a slight, non-significant increase in sinus period duration were observed. Sino-atrial conduction time (SACT) and atrial refractory time were slightly but non-significantly prolonged. AV nodal conduction (AH interval, Wenckebach point) was not significantly altered. Intraventricular conduction (HV interval, QRS duration) remained unchanged.
Electrophysiological Effects in Patients with Sick Sinus Syndrome (SSS): A significant prolongation of SNRT by approximately 80-260 ms was observed, with some cases showing drastic extensions. Global maximum AV conduction was significantly decreased in some patients, and the AH interval was slightly prolonged.
Electrophysiological Effects in Patients with AV Conduction Delays: AV nodal conduction and the effective refractory period (ERP) were prolonged, although no higher-degree AV blocks were observed.
Effects on Heart Rate and Arrhythmias: In patients with sinus tachycardia, Talinolol significantly decreased heart rate (by approximately 15-20%) and AV conduction time, and prolonged refractory periods in the atrium and AV node. In patients with tachycardic atrial fibrillation or flutter, it reduced the ventricular rate by an average of 15-25 bpm. Conversion to sinus rhythm was observed in 42% of patients receiving combination therapy (with quinidine and digitoxin) within 1-6 days (mean 1.73 days).
Effects on Extrasystoles: Talinolol significantly reduced the number of ventricular (VES) and supraventricular (SVES) extrasystoles, particularly in coronary heart disease (CHD) patients, whether exercise-induced or related to increased sympathetic activity. The reduction was approximately 50% for VES and 60% for SVES, an effect comparable to metoprolol. A double-blind trial showed that 300 mg/day talinolol significantly reduced VES and SVES compared to placebo in CHD patients.
Effects in Acute Myocardial Infarction (AMI): In patients treated within the first 6 hours of AMI with a regimen of 10 mg i.v. bolus, 40 mg i.v. infusion over 4 hours, followed by 50 mg orally every 4 hours (300 mg/day), Talinolol was generally well-tolerated. It slightly lowered heart rate and blood pressure. Pulmonary artery pressure was slightly increased after 6 hours compared to a control group (p < 0.05). Cardiac output, peripheral, and pulmonary resistance were slightly enhanced (not significant). Infarct-specific enzymes (ASAT, CK) increased to a lesser degree in the talinolol group compared to the control group, suggesting a reduction in infarct size. Another study in patients treated within the first 48 hours of AMI (10-50 mg i.v. and/or 3x50-100 mg/day orally) reported no deterioration of hemodynamic parameters, even in those with signs of left heart failure, and no negative influence on mortality was observed. [1]

Transcellular Transport in LLC-PK1 Cells: LLC-PK1 cells stably expressing human MDR1, rat Mdr1a, or rat Mdr1b, along with mock-transfected cells, were cultured on Transwell filter inserts for 6 days (MDR1) or 4 days (Mdr1a/Mdr1b). Cell monolayers were pre-incubated in transport medium at 37°C for 30 minutes, and TEER was measured. Transport experiments were initiated by adding talinolol (10 µM) to either the apical or basolateral side. Samples were collected from the opposite side at various time points up to 120 minutes. The apparent permeability coefficient (Papp) was calculated. To confirm P-gp-mediated transport, the inhibitor cyclosporine A (10 µM) was used. For inhibition studies with naringin, the inhibitory effect on MDR1/Mdr1a-mediated transport was assessed by measuring the apical-to-basolateral transport of talinolol (100 µM) in the presence of varying naringin concentrations (10-2000 µM). The effect was expressed as a percentage of control, with 0% control defined by complete inhibition with 10 µM cyclosporine A.
Uptake Study in Xenopus laevis Oocytes: Oocytes were injected with cRNA for human OATP1A2, OATP2B1, or rat Oatp1a5, or with water as a control. After 2-3 days of culture, uptake experiments were performed. Oocytes were pre-incubated in uptake buffer (pH 6.5) at room temperature for 30 minutes, then incubated with talinolol (for time course or concentration-dependence studies). For inhibition studies, oocytes were incubated with talinolol (100 µM) in the presence of varying concentrations of naringin. The uptake reaction was stopped by adding ice-cold buffer, and oocytes were washed, solubilized, and analyzed for talinolol content by LC/MS/MS. Transporter-specific uptake was calculated by subtracting uptake in water-injected oocytes from that in cRNA-injected oocytes. [3]

In Situ Rat Intestinal Closed Loop Method: Male Wistar rats were used. After an overnight fast, rats were anesthetized, and the small intestine (ileum) was exposed. A 10-cm segment of the ileum was isolated by making incisions at both ends and ligated to form a closed loop. The loop was rinsed with saline. Talinolol solution (10 µM, pH 6.5) with or without naringin (200 or 2000 µM), 100% GFJ, or 6-fold diluted GFJ was injected into the loop. After a 5-minute incubation at 37°C, the loop was removed, and the remaining drug solution was collected. The length and radius of the intestinal segment were measured. The amount of talinolol in the collected solution was quantified by LC/MS/MS, and the apparent permeability coefficient was calculated. [3]

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In Situ Rat Intestinal Closed Loop Method: Male Wistar rats were used. After an overnight fast, rats were anesthetized, and the small intestine (ileum) was exposed. A 10-cm segment of the ileum was isolated by making incisions at both ends and ligated to form a closed loop. The loop was rinsed with saline. Talinolol solution (10 µM, pH 6.5) with or without naringin (200 or 2000 µM), 100% GFJ, or 6-fold diluted GFJ was injected into the loop. After a 5-minute incubation at 37°C, the loop was removed, and the remaining drug solution was collected. The length and radius of the intestinal segment were measured. The amount of talinolol in the collected solution was quantified by LC/MS/MS, and the apparent permeability coefficient was calculated. [3]

The paper provides detailed information on the mechanisms affecting the intestinal absorption and bioavailability of talinolol.
Bioavailability: In humans, the oral bioavailability of talinolol is 55 ± 15%. It is noted that less than 1% of an administered dose is found as hydroxylated metabolites in the urine of humans, dogs, and rats, indicating that talinolol is unlikely to be subject to significant metabolism.
Role of Transporters: Intestinal absorption of talinolol is mediated by a interplay of uptake transporters (human OATP1A2 and OATP2B1; rat Oatp1a5) and an efflux transporter (P-gp/MDR1). The net absorption is determined by the balance between these opposing activities.
Effect of Grapefruit Juice (GFJ): The effect of GFJ on talinolol absorption is species-dependent and concentration-dependent due to its component naringin. In humans, naringin inhibits OATP1A2 (IC50 ~343 µM) but not MDR1. Since GFJ naringin concentrations (e.g., ~1200 µM) are not high enough to inhibit MDR1, GFJ predominantly inhibits uptake, leading to reduced talinolol absorption. In rats, naringin inhibits both Oatp1a5 (IC50 ~12.7 µM) and Mdr1a (IC50 ~604 µM). At high naringin concentrations (e.g., ~1200 µM in GFJ), both uptake and efflux are inhibited, but the net effect is increased absorption, primarily due to inhibition of the efflux transporter Mdr1a. At lower concentrations (e.g., ~200 µM in diluted GFJ), only Oatp1a5 is inhibited, leading to decreased absorption. [3]

The literature provides information on side effects, contraindications, and tolerability based on clinical observations.
Contraindications: Absolute contraindications include pronounced bradycardia (including pronounced sick sinus syndrome), higher-degree AV block, bronchial asthma, marked hypotension and shock, and severe cardiac failure.
Side Effects/Tolerability: In a large number of patients, the drug was reported to have good tolerability. Side effects are described as similar to those of other beta-blockers. In combination therapy with other antiarrhythmics (e.g., propafenone, detajmium bitartrate, amiodarone), patients reported good tolerability and no undesired side effects. In one study of patients with tachyarrhythmias and cardiac failure (NYHA II-IV), only one case showed a deterioration of heart failure signs after parenteral administration, while all others showed good effects on arrhythmias with no negative influence on clinical symptoms of failure. In an AMI study, medication was discontinued in two patients due to undesired effects (one with ventricular rhythm, one with shock symptoms). [1]

[1]. Assmann I. The actions of talinolol, a beta 1-selective beta blocker, in cardiac arrhythmia and acute myocardial infarction. Curr Med Res Opin. 1995;13(6):325-42.

[2]. The effects of P-glycoprotein inhibitor zosuquidar on the sex and time-dependent pharmacokinetics of parenterally administered talinolol in mice. Eur J Pharm Sci. 2021 Jan 1;156:105589.

[3]. Species difference in the effect of grapefruit juice on intestinal absorption of talinolol between human and rat. J Pharmacol Exp Ther. 2010 Jan;332(1):181-9.

Talinolol belongs to the urea class of drugs. Talinolol has been used in basic scientific research on gastrointestinal motility disorders.

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Talinolol (Cordanum®) is a cardioselective β₁-adrenoceptor antagonist used for treating various cardiovascular diseases and tachyarrhythmias. It has been used successfully in patients with ventricular and supraventricular tachyarrhythmias related to coronary heart disease (CHD), other cardiovascular diseases, and even hyperthyroidism. Its therapeutic effects are attributed to its ability to depress sinus node automaticity, prolong conduction time in the AV node, and prolong refractory periods in the atrium and AV node.
In the post-infarction phase, it is suggested that Talinolol may reduce myocardial infarct size, likely due to its sympatholytic and antiarrhythmic properties, which protect the heart from sympathetic stimulation. It has been used in combination with other antiarrhythmics (class I agents or amiodarone) for tachyarrhythmias not responding to monotherapy. It can also be used in patients with low-grade or tachyarrhythmia-induced cardiac failure, which is not a contraindication. The literature concludes that the actions of Talinolol correspond to those of other β₁-receptor blockers, and its slight bradycardic effect is considered an advantage, particularly in the acute infarction phase and in many cases of tachyarrhythmia. [1]

363.252

57460-41-0

68770

White to off-white solid powder

1.1±0.1 g/cm3

520.0±50.0 °C at 760 mmHg

160-162ºC

268.3±30.1 °C

0.0±1.4 mmHg at 25°C

1.552

3.2

4

4

8

26

411

0

CC(C)(NCC(O)COC1=CC=C(NC(NC2CCCCC2)=O)C=C1)C

MXFWWQICDIZSOA-UHFFFAOYSA-N

InChI=1S/C20H33N3O3/c1-20(2,3)21-13-17(24)14-26-18-11-9-16(10-12-18)23-19(25)22-15-7-5-4-6-8-15/h9-12,15,17,21,24H,4-8,13-14H2,1-3H3,(H2,22,23,25)

1-(4-(3-(tert-butylamino)-2-hydroxypropoxy)phenyl)-3-cyclohexylurea

Talinolol Cordanum

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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 (~275.11 mM)

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.)