• YAKHAK HOEJI
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• v.29 no.1
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• pp.11-17
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• 1985

The behavioral effects of propranolol (60mg/kg) and metoprolol (100mg/kg) each alone and coadministered orally with cinnarizine (100mg/kg) were investigated and compared with each of betablockers alone treated group in rodents. Propranolol showed depressive effects through locomotor activity, conditioned avoidance response, rota-rod test, traction test, and analgesic effect in mice. When combined with cinnarizine and propranolol, the behavioral depressive effect of propranolol was reduced comparing with propranolol alone treated group. However, metoprolol alone or combined with cinnarizine didn't showed any behavioral depressive effect so much as propranolol.

• Journal of Chest Surgery
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• v.19 no.2
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• pp.197-208
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• 1986

Propranolol is one of clinically useful antiarrhythmic agents and electrophysiologically classified as group II. And the negative inotropic effect which is not related to adrenolytic effect has been demonstrated with high concentration of propranolol. On the other hand, it has been well known that the calcium plays a central role in excitation-contraction coupling process of myocardium and also in electrophysiological changes of cell membrane. Author studies the effect of propranolol on calcium uptake and release in sarcoplasmic reticulum and mitochondria prepared from porcine myocardium to investigate the mechanism of action of propranolol on myocardium. The results are summarized as follow: 1] The maximum Ca++-uptake of sarcoplasmic reticulum is inhibited by propranolol in a dose dependent manner. 2] The release of calcium from sarcoplasmic reticulum is not affected by propranolol but with higher than 1x10-3 M of propranolol, rate of calcium release from sarcoplasmic reticulum is decreased. 3] Propranolol inhibits the maximum uptake and uptake rate of calcium in mitochondria non-competitively. [Ki = 6.21 x 10-4 M] 4] The rate of Na+ induced calcium release from mitochondrion shows a function of [Na+]2 and is inhibited by propranolol with the concentration significantly lower than that affect the calcium uptake in sarcoplasmic reticulum and in mitochondria [Ki = 2.91 x 10-5 M]. These results suggest that propranolol affects the intracellular calcium homeostasis which may considered to be one of the mechanism of action of propranolol on myocardium.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.219-231
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• 1995

Vasoactive intestinal polypeptide(VIP) and ${\beta}-adrenergic$ agonists have immunomodultory effects on the peripheral blood T-lymphocytes of rat through their own receptors. Both of them utilize the same signal transduction pathway. That is, the stimulatory guanine nucleotide binding protein(G protein) mediates the receptor-adenylyl cyclase coupling, producing intracellular increase of cyclic adenosine monophosphate(cAMP). In the previous experiment, propranolol, a ${\beta}-adrenergic$ receptor blocker, inhibited the VIP-induced protein phosphorylation in lymphocytes. However, propranolol could not block the effect induced by forskolin. Therefore, this study was designed to elucidate the mechanism of the inhibitory action of propranolol on the effects of VIP. Using peripheral blood lymphocytes of rats, the effect of propranolol on the receptor binding characteristics of VIP was observed. And the effects of propranolol were compared to the effects of timolol on the cAMP increase induced by isoproterenol, VIP or forskolin. The results obtained are as follows. 1) Receptor binding study showed no significant differences in the affinity or density of VIP receptor between the control and propranolol-pretreated groups. 2) VIP-induced increase of cAMP was inhibited by propranolol, but not by timolol. 3) Both propranolol and timolol suppressed the isoproterenol-induced cAMP increase. 4) Propranolol also inhibited the histamine-induced cAMP increase. 5) Propranolol did not inhibit the increase of cAMP stimulated by forskolin. 6) Lidocaine did not block the VIP-induced cAMP increase. These results show that the inhibitory mechanism of propranolol is not related to ${\beta}-adrenergic$ receptor or its membrane stabilizing effect, and it is suggested that propranolol can block the effects of VIP by inhibiting the intermediate step between the VIP receptor and adenylyl cyclase.

• Journal of Pharmaceutical Investigation
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• v.20 no.4
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• pp.199-203
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• 1990

The pharmacokinetics of propranolol administered orally (10 me/kg) was investgated in the rabbits of carbon tetrachloride induced hepatic failure. The plasma concentration and relative bioavailability of propranolol were increased significantly in hepatic failure rabbits, compared with those of normal rabbits. There were significant relationship between GOT, GPT value and bioavailability parameters of propranolol. In short, dosage regimen of propranolol is considered to be adjusted in dose size and dosing interval using GOT or GPT an index.

• Clinical and Experimental Pediatrics
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• v.55 no.5
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• pp.164-170
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• 2012

Purpose: Dramatic improvement of hemangioma to propranolol has been recently reported; however, details on dose and duration of treatment, potential risks, and monitoring have not been determined. The objective of this study is to describe and analyze the use of propranolol as a first-line treatment or as a single therapy in management of complicated hemangioma. Methods: A retrospective chart review of eight patients diagnosed with hemangioma and treated with propranolol in Kangbuk Samsung Hospital from February 2010 to April 2011 was performed. Results: Eight patients with hemangioma with functional impairment, cosmetic disfigurement, or rapid growth were treated with propranolol. Five patients had solitary facial hemangioma. The mean age of symptoms at onset was 5 weeks. The median age for starting propranolol treatment was 5.5 months. Propranolol at 2 mg/kg/day was finally administered in divided doses with a gradual increase. Significant regression was observed in seven patients, and shrinkage in size, softening in consistency, and decrease in redness were evident within 4 weeks. Among them, six patients were still taking propranolol, and one patient had stopped after 12 months. Other one patient did not show significant improvement with satisfactory result after 3 months of propranolol use. Treatment with propranolol was well tolerated and had few side effects. No rebound growth was observed in any of the patients. Conclusion: We observed that use of propranolol was very effective in treatment of hemangioma without obvious adverse effects or relapse.

• YAKHAK HOEJI
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• v.28 no.5
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• pp.257-263
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• 1984

In our former report we observed that cinnarizine influenced the antihypertensive effect of propranolol beneficially, but not of metoprolol in SHR and normal cat. Cardiac contractilities and smooth muscle relaxations induced by above drugs were measured to elucidate their mechanism of action. In cinnarizine and propranolol treated group, both of negative inotropic and ${\beta}-blocking$ activity of propranolol in perfused rat hearts were increased and propranolol induced contraction in isolated arterial and trachea smooth muscle of the guinea pig was antagonized comparing to propranolol alone treated group. However, in the cinnarizine and metoprolol treated group, no significant differences in activity on the above were observed compared to metoprolol alone treated group.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.26 no.1
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• pp.70-77
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• 2023

Hepatic hemangiomas (HH) - classified into congenital hepatic hemangiomas (CHH) or infantile hepatic hemangiomas (IHH) - are benign vascular tumors that are mainly asymptomatic, but may cause clinical problems that require treatment. While focal, multifocal, and diffuse IHH are responsive to propranolol treatment, CHH is mainly focal and thought to be resistant to treatment with propranolol. The clinical and imaging distinctions between CHH and IHH in cases of focal lesions can be challenging, while histopathological distinction is mostly lacking in the clinical setting. We report 4 neonatal symptomatic cases of focal HH treated with propranolol, with partial or complete resolution of the tumor, and the positive hemodynamic effect of propranolol in one case. We believe that although clear differentiation cannot be achieved between CHH and IHH without histopathological examination in cases of focal HH in neonates, propranolol treatment should be attempted in symptomatic cases since its benefits outweigh the possible small risk of side effects of propranolol.

• Journal of Korean Neurosurgical Society
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• v.64 no.5
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• pp.716-725
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• 2021

Objective : The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process. Methods : We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma. Results : Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA. Conclusion : These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation.

• Environmental Analysis Health and Toxicology
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• v.9 no.1_2
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• pp.9-17
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• 1994

The Ha-antagonist, cimetidine, has been shown to retard the hepatic elimination of low and high clearance drugs, and this has been attributed to inhibition of microsomal cytochrome P-450. This study was done to determine the effects of low (50$\mu\textrm{g}$) and high (1mg) dose of famotidine, another histamine H$_2$-receptor antagonist, on hepatic elimination of propranolol compared with cimetidine in the isolated perfused rat liver. Both low and high dose of cimetidine not only inhibited the elimination of propranolol but also increased the area under the perfusate propranolol concentration time curve (AUC). In contrast, low and high dose of famotidine did not affect hepatic elimination of propranolol. Our findings suggest that famotidine has not a propensity for hepatic microsomal inhibition.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.379-383
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• 1991

This study was attempted to investgate the pharmacokinetics of theophylline (4 mg/kg i.v) in the rabbits pretreated with propranolol (1 and 2.5 mg/kg/hr, infusion) for four hours. The plasma concentration and AUC of theophylline were increased in rabbits pretreated with propranolol as compared with those of normal rabbits. The amount of cumulative urinary excretion and renal clearance and total body clearance were decreased in rabbits pretreated with propranolol as compared with those of normal rabbits. The apparent volume of distribution was slightly affected by change of the clearance of theophylline. From the results of this experiment, it is desirable that dosage regimen of theophylline should be adjusted when theophylline combined with propranolol in clinical pharmacy practice.