Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new inderal research articles will be listed here shortly after becoming available to us.
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Medical research on inderal
Characterization of rat heart alkaline phosphatase isoenzymes and modulation of activity.
Braz J Med Biol Res. 2008 Jul; 41(7): 600-9
Mota A, Silva P, Neves D, Lemos C, Calhau C, Torres D, Martel F, Fraga H, Ribeiro L, Alçada MN, Pinho MJ, Negrão MR, Pedrosa R, Guerreiro S, Guimarães JT, Azevedo I, Martins MJ
Alkaline phosphatase (ALP) is important in calcification and its expression seems to be associated with the inflammatory process. We investigated the in vitro acute effects of compounds used for the prevention or treatment of cardiovascular diseases on total ALP activity from male Wistar rat heart homogenate. ALP activity was determined by quantifying, at 410 nm, the p-nitrophenol released from p-nitrophenylphosphate (substrate in Tris buffer, pH 10.4). Using specific inhibitors of ALP activity and the reverse transcription-polymerase chain reaction, we showed that the rat heart had high ALP activity (31.73 +/- 3.43 nmol p-nitrophenol.mg protein-1.min-1): mainly tissue-nonspecific ALP but also tissue-specific intestinal ALP type II. Both ALP isoenzymes presented myocardial localization (striated pattern) by immunofluorescence. ALP was inhibited a) strongly by 0.5 mM levamisole, 2 mM theophylline and 2 mM aspirin (91, 77 and 84%, respectively) and b) less strongly by 2 mM L-phenylalanine, 100 mL polyphenol-rich beverages and 0.5 mM progesterone (24, 21 to 29 and 11%, respectively). beta-estradiol and caffeine (0.5 and 2 mM) had no effect; 0.5 mM simvastatin and 2 mM atenolol activated ALP (32 and 36%, respectively). Propranolol (2 mM) tended to activate ALP activity and corticosterone activated (18%) and inhibited (13%) (0.5 and 2 mM, respectively). We report, for the first time, that the rat heart expresses intestinal ALP type II and has high total ALP activity. ALP activity was inhibited by compounds used in the prevention of cardiovascular pathology. ALP manipulation in vivo may constitute an additional target for intervention in cardiovascular diseases.
Yao Xue Xue Bao. 2008 May; 43(5): 467-73
Jiang XZ, Li YF, Zhang YZ, Chen HX, Li J, Wang NP
This study is to explore the possible mechanisms of the antidepressant-like effect of agmatine. By using two traditional "behavior despair" model, tail suspension test and forced swimming test, we examined the effects of some monoamine receptor antagonists (including beta-adrenergic receptor antagonist propranolol, beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol, alpha2-adrenergic receptor antagonists yohimbine and idazoxan and 5-HT3 receptor antagonist tropisetron) on the antidepressant-like action of agmatine in mice. Activity of adenylate cyclase (AC) in the synapse membrane from rat frontal cortex was determined by radioimmunoassay. Single dose of agmatine (5-40 mg x kg(-1), ig) dose-dependently decrease the immobility time in tail suspension test in mice, indicating an antidepressant-like effect. The effect of agmatine (40 mg x kg(-1), ig) was antagonized by co-administration of beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol (20 mg x kg(-1), ip), alpha2-adrenergic receptor antagonists yohimbine (5-10 mg x kg(-1), ip) or idazoxan (4 mg x kg(-1), ip), but not beta-adrenergic receptor antagonist propranolol (5-20 mg x kg(-1), ip) and 5-HT3 receptor antagonist tropisetron (5-40 mg x kg(-1), ip). Agmatine (5-40 mg x kg(-1), ig) also dose-dependently decrease the immobility time in forced swimming test in mice. The effect of agmatine (40 mg x kg(-1), ig) was also antagonized by pindolol (20 mg x kg(-1), ip), yohimbine (5-10 mg x kg(-1), ip), or idazoxan (4 mg x kg(-1), ip). Incubation of agmatine (0.1-6.4 micromol x L(-1)) with the synaptic membrane extracted from rat frontal cortex activated the AC in a dose-dependent manner in vitro. While the effect of agmatine (6.4 micromol x L(-1)) was dose-dependently antagonized by pindolol (1 micromol x L(-1)) or yohimbine (0.25-1 micromol x L(-1)). Chronic treatment with agmatine (10 mg x kg(-1), ig, bid, 2 w) or fluoxetine (10 mg x kg(-1), ig, bid, 2 w) increased the basic activity, as well as the Gpp (NH)p (1-100 micromol x L(-1)) stimulated AC activity in rat prefrontal cortex. These results indicate that regulation on 5-HT1A/1B and alpha2 receptors, and activation AC in the frontal cortex is one of the important mechanisms involving in agmatine's antidepressant-like action.
Beat-to-beat QT interval variability is primarily affected by the autonomic nervous system.
Ann Noninvasive Electrocardiol. 2008 Jul; 13(3): 228-33
Mine T, Shimizu H, Hiromoto K, Furukawa Y, Kanemori T, Nakamura H, Masuyama T, Ohyanagi M
BACKGROUND: Beat-to-beat QT interval variability is associated with life-threatening arrhythmias and sudden death, however, its precious mechanism and the autonomic modulation on it remains unclear. The purpose of this study was to determine the effect of drugs that modulate the autonomic nervous system on beat-to-beat QT interval. METHOD: RR and QT intervals were determined for 512 consecutive beats during fixed atrial pacing with and without propranolol and automatic blockade (propranolol plus atropine) in 11 patients without structural heart disease. Studied parameters included: RR, QTpeak (QRS onset to the peak of T wave), QTend (QRS onset to the end of T wave) interval, standard deviation (SD) of the RR, QTpeak, and QTend (RR-SD, QTpeak-SD, and QTend-SD), coefficients of variation (RR- CV, QTpeak-CV, and QTend-CV) from time domain analysis, total power (TP; RR-TP, QTpeak-TP, and QTend-TP), and power spectral density of the low-frequency band (LF; RR-LF, QTpeak-LF, and QTend-LF) and the high-frequency band (HF; RR-HF, QTpeak-HF and QTend-HF). RESULTS: Administration of propranolol and infusion of atropine resulted in the reduction of SD, CV, TP, and HF of the QTend interval when compared to controlled atrial pacing (3.7 +/- 0.6 and 3.5 +/- 0.5 vs 4.8 +/- 1.4 ms, 0.9 +/- 0.1 and 0.9 +/- 0.1 vs 1.2 +/- 0.3%, 7.0 +/- 2.2 and 7.0 +/- 2.2 vs 13.4 +/- 8.1 ms(2), 4.2 +/- 1.4 and 4.2 +/- 1.2 vs 8.4 +/- 4.9 ms(2), respectively). Administration of propranolol and atropine did not affect RR interval or QTpeak interval indices during controlled atrial pacing. CONCLUSIONS: Beat-to-beat QT interval variability is affected by drugs that modulate the autonomic nervous system.
A double-blind, randomized trial of low-dose topiramate vs propranolol in migraine prophylaxis.
Acta Neurol Scand. 2008 Aug 16;
Ashtari F, Shaygannejad V, Akbari M
Objective - To assess the efficacy and safety of low-dose topiramate in migraine prophylaxis vs propranolol. Patients and methods - A randomized, double-blind, clinical trial including 62 patients with frequent migraine headaches (>/= 3 attacks per month) was performed for a period of 8 weeks. The patients were randomly divided into two treatment groups - treated by topiramate 50 mg/day and propranolol 80 mg/day, respectively. The patients were assessed at 0, 4, and 8 weeks of the study. Results - The topiramate group showed a reduction in the mean (+/-SD) of monthly migraine frequency from 6.07 (+/-1.89) to 1.83 (+/-1.39) episodes per month, headache intensity from 7.1 (+/-1.45) to 3.67 (+/-2.1) based on the Visual Analog Scale, and headache duration from 16.37 (+/-7.26) to 6.23 (+/-5.22) hours (P < 0.001). In the patients treated with propranolol, the mean (+/-SD) of monthly headache frequency declined from 5.83 (+/-1.98) to 2.2 (+/-1.67) per month, headache intensity lessened from 6.43 (+/-1.6) to 4.13 (+/-1.94) and headache duration decreased from 15.10 (+/-6.84) to 7.27 (+/-6.46) h (P < 0.001). Conclusion - This study demonstrated that both low-dose topiramate and propranolol could significantly reduce migraine headache frequency, intensity, and duration. However, compared with propranolol, low-dose topiramate showed better results.
Life Sci. 2008 Jul 25;
Campos-Bedolla P, Vargas MH, Segura P, Carbajal V, Calixto E, Figueroa A, Flores-Soto E, Barajas-López C, Mendoza-Patiño N, Montaño LM
AIMS: Although 5-hydroxytryptamine (5-HT) contracts airway smooth muscle in many mammalian species, in guinea pig and human airways 5-HT causes a contraction followed by relaxation. This study explored potential mechanisms involved in the relaxation induced by 5-HT. MAIN METHODS: Using organ baths, patch clamp, and intracellular Ca(2+) measurement techniques, the effect of 5-HT on guinea pig airway smooth muscle was studied. KEY FINDINGS: A wide range of 5-HT concentrations caused a biphasic response of tracheal rings. Response to 32 muM 5-HT was notably reduced by either tropisetron or methiothepin, and almost abolished by their combination. Incubation with 10 nM ketanserin significantly prevented the relaxing phase. Likewise, incubation with 100 M charybdotoxin or 320 nM iberiotoxin and at less extent with 10 muM ouabain caused a significant reduction of the relaxing phase induced by 5-HT. Propranolol, L-NAME and 5-HT(1A), 5-HT(1B)/5-HT(1D) and 5-HT(2B) receptors antagonist did not modify this relaxation. Tracheas from sensitized animals displayed reduced relaxation as compared with controls. In tracheas precontracted with histamine, a concentration response curve to 5-HT (32, 100 and 320 muM) induced relaxation and this effect was abolished by charybdotoxin, iberiotoxin or ketanserin. In single myocytes, 5-HT in the presence of 3 mM 4-AP notably increased the K(+) currents (I(K(Ca))), and they were completely abolished by charybdotoxin, iberiotoxin or ketanserin. SIGNIFICANCE: During the relaxation induced by 5-HT two major mechanisms seem to be involved: stimulation of the Na(+)/K(+)-ATPase pump, and increasing activity of the high-conductance Ca(2+)-activated K(+) channels, probably via 5-HT(2A) receptors.
An Investigation into the Influence of Counterion on the Properties of Some Amorphous Organic Salts.
Mol Pharm. 2008 Aug 16;
Towler CS, Li T, Wikström H, Remick DM, Sanchez-Felix MV, Taylor LS
Amorphous solids and crystalline salts are both of interest as a means of improving the dissolution characteristics and apparent solubility of poorly water soluble active pharmaceutical ingredients which have low bioavailability in humans. The theory and selection of both crystalline drug substance salt forms and amorphous products have been extensively studied. However, less is known about the impact of different counterions on the properties of amorphous drug substance salts. In this study, several salts of either nicardipine or propranolol were prepared and characterized with respect to glass transition temperature, crystallization tendency and moisture sorption behavior. Although the moisture sorption behavior and crystallization tendency varied depending on the counterion used, no trends were readily apparent. The glass transition temperature was found to be dependent on the counterion used to form the salt, and was higher in all instances for the salts than for the neutral compound. Several molecular descriptors were calculated for the various counterions, and multivariate analysis was used to build a model that successfully correlated T g with a number of these parameters. Important parameters which influenced T g included counterion p K a and electrophilicity index. In conclusion, it is apparent that, as for crystalline salts, the counterion has an effect on the properties of amorphous materials.
Basic Clin Pharmacol Toxicol. 2008 Aug 11;
Andrzejczak D, Kocon K, Zięba R
Mirtazapine is a noradrenergic and specific serotonergic antidepressant. The influence of the drug on the cardiovascular system has not been definitely determined. Therefore, we made an attempt to evaluate the influence of chronic administration of mirtazapine on the hypotensive action of a single administered dose of propranolol and enalapril in spontaneously hypertensive rats. The animals were divided into eight experimental groups. Mirtazapine (5 and 10 mg/kg) was administered intraperitoneally for 14 days. Twenty-four hours after the last administration of the drug, the rats received a single intraperitoneal dose of hypotensive drugs (propranolol 5 mg/kg or enalapril 10 mg/kg) or 1% solution of methylcellulose. Mirtazapine administered chronically did not affect the hypotensive effect of a single dose of propranolol or enalapril in spontaneously hypertensive rats. It seems that mirtazapine could be a useful drug in patients with depression accompanied by hypertension.
Gastric motility evaluated by electrogastrography and alternating current biosusceptometry in dogs.
Physiol Meas. 2008 Aug 13; 29(9): 1023-1031
Andreis U, Américo MF, Corá LA, Oliveira RB, Baffa O, Miranda JR
Association techniques could be the answer for evaluating electromechanical coupling and gastric emptying under basal conditions and after administration of drugs. Electrogastrography (EGG) and alternating current biosusceptometry (ACB) emerged due to their interesting nature, noninvasiveness and low cost. The aims were to examine in dogs the effect of erythromycin on gastric emptying by ACB and electrical and motor responses to erythromycin and propranolol by ACB and EGG respectively. Twelve beagle dogs ingested a solid test meal on separate days. Under anesthesia, gastric motility was evaluated by EGG and ACB after erythromycin and propranolol administration. Without anesthesia, gastric emptying was assessed under basal conditions and after erythromycin by ACB. ACB and EGG showed a strong temporal correlation. Erythromycin and propranolol presented the same profile with different power ratios; the amplitude increased whereas frequency decreased. Also, erythromycin administration hastened gastric emptying while reducing the orocaecal transit time. There is a demand for reliable, easy-to-perform and comfortable techniques to record gastric emptying and gastric activity in medicine and veterinary practice. In summary, the association of ACB with EGG accompanied by an appropriate animal model is promising for evaluating effects of drugs in gastric myoelectrical and contractile activity.
Mechanism of vasorelaxant activity of a fraction of root extract of Sesamum indicum Linn.
Indian J Exp Biol. 2008 Jun; 46(6): 457-64
Suresh Kumar P, Patel JS, Saraf MN
The petroleum ether soluble fraction (SIPE) of the root extract of S. indicum was evaluated for the vasorelaxant activity using isolated rat aorta. SIPE up to 180 microg/ml concentration significantly inhibited phenylephrine- and KCl-induced contraction to the extent of 98.13 +/- 6.37 and 70.19 +/- 3.43% respectively in isolated rat aorta in a concentration dependent manner. The vasorelaxant activity was not blocked by propranolol (10 microM), atropine (1 microM) indomethacin (10 microM) and glibenclamide (10 microM). Influence of SIPE on phenylephrine-induced contractions in aortic preparations in absence of functional endothelium and on pre-incubating the tissue with L-NAME (300 microM) or methylene blue (10 microM) was also studied. SIPE at 180 microg/ml concentration could elicit partial relaxation in presence of L-NAME or methylene blue to the extent of 34.26 +/- 6.13 and 25.66 +/- 10.95% respectively. However, in absence of functional endothelium, SIPE exhibited little relaxation to the extent of 6.70 +/- 4.87%. These studies revealed that the vasorelaxant activity of SIPE was chiefly mediated through endothelium-dependent pathway.
Expert Opin Investig Drugs. 2008 Sep; 17(9): 1281-99
Graham S, Hammond-Jones D, Gamie Z, Polyzois I, Tsiridis E, Tsiridis E
BACKGROUND: beta-Adrenergic receptor antagonists (beta-blockers) have a well-recognised antihypertensive action that is mediated through a reduction in cardiac output and in the release of renin from the kidneys and inhibition of the action of endogenous catecholamines on beta-adrenergic receptors. This class of drugs has been shown to reduce the incidence of cardiovascular disease. Recent evidence suggests that beta-blockers may also have an effect on bone structure, metabolism and fracture healing. OBJECTIVE: This paper reviews in vitro and in vivo data that suggest beta-blockers have primarily an anabolic effect on bone metabolism. RESULTS: The sympathetic nervous system has a catabolic effect on bone, and in vitro studies have shown that adrenergic agonists stimulate bone resorption. The beta-blocker propranolol has been shown to increase bone formation in ovariectomised female rats. Also, recent observational clinical studies provide evidence to show that beta-blockers are associated with reduction in fracture risk in both men and women. CONCLUSION: Although there are some controversial studies, most research concludes that beta-blockers show promise in the treatment of osteoporosis and fracture healing.