Bupranolol
(Synonyms: 布拉洛尔) 目录号 : GC62648
A β-AR antagonist
Cas No.:14556-46-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Bupranolol is an antagonist of β-adrenergic receptors (β-ARs; Kis = 6-15 nM for β1- and β2-ARs).1 In vivo, bupranolol (10 ?mol/kg) reduces heart rate and diastolic blood pressure in pithed rats.2
1.Wellstein, A., Küppers, H., Pitschner, H.F., et al.Transdermal delivery of bupranolol: Pharmacodynamics and beta-adrenoceptor occupancyEur. J. Clin. Pharmacol.31(4)419-422(1986) 2.Malinowska, B., Kie?-Kononowicz, K., Flau, K., et al.Atypical cardiostimulant β-adrenoceptor in the rat heart: Stereoselective antagonism by bupranolol but lack of effect by some bupranolol analoguesBr. J. Pharmacol.139(8)1548-1554(2003)
| Cas No. | 14556-46-8 | SDF | |
| 别名 | 布拉洛尔 | ||
| 分子式 | C14H22ClNO2 | 分子量 | 271.78 |
| 溶解度 | DMSO : 50 mg/mL (183.97 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.6794 mL | 18.3972 mL | 36.7945 mL |
| 5 mM | 0.7359 mL | 3.6794 mL | 7.3589 mL |
| 10 mM | 0.3679 mL | 1.8397 mL | 3.6794 mL |
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Interactions of Bupranolol with the polymorphic debrisoquine/sparteine monooxygenase (CYP2D6)
Eur J Clin Pharmacol 1993;45(3):261-4.PMID:8276051DOI:10.1007/BF00315393.
The beta-adrenoceptor blocker Bupranolol turned out to be a competitive inhibitor of the polymorphic cytochrome P450 CYP2D6 of which sparteine is a substrate. There was stereo-selectivity of Bupranolol involved: (-)-bupranolol was the weakest inhibitor with an apparent Ki value of 1.32 microM, (+)-bupranolol was the most potent with an apparent Ki value of 0.55 microM, while the therapeutically used racemic Bupranolol had an intermediate value of 0.88 microM. A 10 min pre-incubation of 5 microM Bupranolol with the enzyme preparation prior to the addition of substrate, reduced the inhibition of sparteine metabolism from 52 to about 25%. This suggests that--during these inhibition studies--bupranolol was much more rapidly metabolized than was sparteine, so that the measured Ki values must represent overestimates. The enzyme catalysing Bupranolol metabolism was CYP2D6: microsomes from a liver with the genetic enzyme deficiency did not metabolize Bupranolol; in microsomes from livers containing the enzyme and 10 microM Bupranolol, 5 microM quinidine caused a 72% inhibition of Bupranolol metabolism. Although our methods were not sufficiently sensitive to measure the Km of Bupranolol directly, it is undoubtedly the beta-adrenoceptor blocker with the highest-known apparent affinity for CYP2D6. High affinity and rapid metabolism are infrequent combinations in enzymology.
Differences in the Antinociceptive Effects and Binding Properties of Propranolol and Bupranolol Enantiomers
J Pain 2015 Dec;16(12):1321-1333.PMID:26456674DOI:10.1016/j.jpain.2015.09.004.
Recent efforts have suggested that the β-adrenergic receptor (β-AR) system may be a novel and viable therapeutic target for pain reduction; however, most of the work to date has focused on the β(2)-adrenergic receptor (AR). Here, we compared the antinociceptive effects of enantiomeric configurations of propranolol and Bupranolol, two structurally similar nonselective β-blocking drugs, against mouse models of inflammatory and chronic pain. In addition, we calculated in silico docking and measured the binding properties of propranolol and Bupranolol for all 3 β-ARs. Of the agents examined, S-bupranolol is superior in terms of its antinociceptive effect and exhibited fewer side effects than propranolol or its associated enantiomers. In contrast to propranolol, S-bupranolol exhibited negligible β-AR intrinsic agonist activity and displayed a full competitive antagonist profile at β(1)/β(2)/β(3)-ARs, producing a unique blockade of β(3)-ARs. We have shown that S-bupranolol is an effective antinociceptive agent in mice without negative side effects. The distinctive profile of S-bupranolol is most likely mediated by its negligible β-AR intrinsic agonist activity and unique blockade of β(3)-AR. These findings suggest that S-bupranolol instead of propranolol may represent a new and effective treatment for a variety of painful conditions. Perspective: The S enantiomer of Bupranolol, a β-receptor antagonist, shows greater antinociceptive efficacy and a superior preclinical safety profile and it should be considered as a unique β-adrenergic receptor compound to advance future clinical pain studies.
Atypical cardiostimulant beta-adrenoceptor in the rat heart: stereoselective antagonism by Bupranolol but lack of effect by some Bupranolol analogues
Br J Pharmacol 2003 Aug;139(8):1548-54.PMID:12922943DOI:10.1038/sj.bjp.0705390.
1. Atypical beta-adrenoceptors resistant to propranolol, but blocked by Bupranolol, increase contractile force and/or frequency of the heart in humans and rats. We compared the potencies of the enantiomers of Bupranolol and examined the possible effects of seven Bupranolol analogues including bevantolol (BEV) at this receptor in pithed and vagotomized rats. 2. CGP 12177, an agonist of the atypical beta-adrenoceptor, increased heart rate dose-dependently. Its dose-response curve was shifted to the right by S-(-)-bupranolol 10 micro mol kg(-1) by a factor of 8.4, but not affected by the same dose of R-(+)-bupranolol. 3. Desmethylbupranolol and compounds BK-21, BK-22, BK-23 and BK-25 also increased heart rate dose-dependently. The beta(1)-adrenoceptor antagonist CGP 20712 given in combination with the beta(2)-adrenoceptor antagonist ICI 118,551 (0.1 micro mol kg(-1) each) reduced the positive chronotropic action of the five Bupranolol analogues without affecting that of CGP 12177. The potencies of the Bupranolol analogues to increase heart rate were correlated (r=0.91, P<0.05) with their affinities for beta(1)-adrenoceptor binding sites in rat brain cortex membranes labelled with [(3)H]CGP 12177 (in the presence of ICI 118,551). 4. BK-26 and BEV, 10 micro mol kg(-1) each, had only minor effects on heart rate by themselves and did not antagonize the effect of CGP 12177. However, at 1 micro mol kg(-1), they antagonized the increase in heart rate elicited by the beta(1)-adrenoceptor agonist prenalterol. 5. In conclusion, Bupranolol is a stereoselective antagonist at the atypical cardiostimulant beta-adrenoceptor. The effects of the Bupranolol analogues are related to the activation or blockade of beta(1)-adrenoceptors, but not of atypical beta-adrenoceptors.
Evidence that (+)-bupranolol interacts directly with myocardial beta-adrenoceptors. Control of optical purity with differential thermal analysis
Naunyn Schmiedebergs Arch Pharmacol 1980 Aug;313(1):1-8.PMID:6259541DOI:10.1007/BF00505796.
Melting points measured with the capillary method were 150.5 degree C, 150.5 degree C and 224.0 degree C for hydrochlorides of (+)-bupranolol, (-)-bupranolol and (+/-)-bupranolol, respectively. The large difference in melting points of 73.5 degree C prompted us to determine possible contaminations of (+)-bupranolol with traces of (-)-bupranolol using differential scanning calorimetry. We detected as little as 0.001% (-)-bupranolol in a standard mixture of (+)-bupranolol and (-)-bupranolol. A batch of (+)-bupranolol not measurably contaminated with (-)-bupranolol (optically purity greater than 99.999%) was used in pharmacological and biochemical assays. The affinities of (-)-bupranolol and (+)-bupranolol were determined functionally by the blockade of isoprenaline stimulation of spontaneously beating rat right atria and electrically driven kitten papillary muscles; and directly by inhibition of binding of 3H-(-)-propranolol to kitten ventricle membrane particles. In all 3 systems the enantiomeric (-)/(+) affinity ratio was 50--120 for Bupranolol. These experiments prove that (+)-bupranolol itself binds to the beta-adrenoceptors of mammalian myocardium.
Polymer based solutions of Bupranolol hydrochloride for intranasal systemic delivery
J Drug Target 2011 Apr;19(3):204-11.PMID:20550434DOI:10.3109/1061186X.2010.492520.
The present study was aimed at developing intranasal polymer based solutions as alternative route for systemic delivery of Bupranolol hydrochloride (BPH). It is a potent β-blocker drug which upon oral administration undergoes extremely high hepatic first-pass metabolism (>90% in humans). The polymeric solutions were prepared using varying concentrations of polymers like sodium alginate, chitosan, sodium carboxymethylcellulose, methylcellulose (MC), polyvinyl alcohol, carbopol, hydroxypropyl MC, and hydroxypropyl cellulose. The prepared formulations were evaluated in terms of pH of the solution, angular viscosity, drug content, gel strength, gelation temperature, in vitro drug release, in vivo pharmacodynamic studies, histopathological, and stability studies. Except MC based solutions, a biphasic pattern of drug release was obtained in all other cases. Nasal administration of selected batches of polymeric solutions were found to be nontoxic and were able to improve drug bioavailability when compared to oral, nasal, and intravenous solution administrations of BPH.