Abstract:
:Intravenous amiodarone (Amiodarone i.v.) is widely used to treat cardiac arrhythmias. The most frequent clinical adverse event associated with Amiodarone i.v. administration is systemic hypotension which has been attributed to the cosolvents used in the formulation, polysorbate 80 and benzyl alcohol. To minimize hypotension Amiodarone i.v. is diluted in 5% dextrose in water prior to administration and slowly infused. PM101 is a novel intravenous formulation that uses sulfobutylether-7-beta-cyclodextrin to solubilize amiodarone, and thus should be devoid of the untoward hemodynamic effects associated with polysorbate 80 and benzyl alcohol. Beagle dogs (n=7/group) were anesthetized with morphine and alpha-chloralose and instrumented to assess aortic blood pressure, cardiac output, cardiac contractility, and heart rate. Animals were treated with the U.S. approved human-equivalent loading dose (2.14 mg/kg) of Amiodarone i.v., PM101, and their respective vehicle controls. Administration of Amiodarone i.v. rapidly and significantly decreased mean aortic pressure, cardiac output, and cardiac contractility. A significant increase in heart rate was also observed as was a transient, but not significant, decrease in systemic vascular resistance. A similar pattern of rapid and significant hemodynamic changes was produced by the Amiodarone i.v. Vehicle (polysorbate 80/benzyl alcohol) alone. In marked contrast, PM101 and its vehicle produced no significant hemodynamic effects. This study provides a useful model for the continued search for a safe and effective intravenous amiodarone formulation devoid of the hypotensive risk associated with the current commercial formulation.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Cushing DJ,Kowey PR,Cooper WD,Massey BW,Gralinski MR,Lipicky RJdoi
10.1016/j.ejphar.2009.02.009subject
Has Abstractpub_date
2009-04-01 00:00:00pages
167-72issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(09)00148-4journal_volume
607pub_type
杂志文章abstract::The effect of 5-hydroxytryptamine (5-HT) on the release of prostacyclin and thromboxane (TX) A2 from isolated rat dental pulp was evaluated. 5-HT (1-1,000 microM) caused a dose-dependent and marked stimulation of the release of prostacyclin but not TXA2. Of the 5-HT-related indolealkylamines tested, only tryptamine ha...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90320-7
更新日期:1987-04-29 00:00:00
abstract::The biological activity of two galanin (GAL) fragments, GAL-(1-16) and GAL-(17-29), was tested in vivo by using a spinal nociceptive flexor reflex model in the rat. Intrathecal (i.t.) GAL-(1-16) had a similar biphasic effect on the flexor reflex, with facilitation at lower doses and facilitation followed by depression...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90502-w
更新日期:1990-06-21 00:00:00
abstract::The coronary vasoconstrictor effect of endothelin-1 was characterized in the isolated rat heart by using the endothelin ETA receptor antagonist D-Asp-L-Pro-D-Val-L-Leu-D-Trp (BQ-123) and the endothelin ETB receptor antagonist [Cys11-Cys15]endothelin-1-(11-21) (IRL 1038). In addition, the involvement of nitric oxide an...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90260-7
更新日期:1994-12-12 00:00:00
abstract::Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, is found in the central nervous system as well as in the heart. CGRP shows high sequence homology with amylin, salmon calcitonin, and adrenomedullin. This study aimed to investigate the effect of CGRP on atrial hemodynamics and atrial natriuretic pe...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2003.10.020
更新日期:2004-01-12 00:00:00
abstract::The kinetics of [3H]dexetimide dissociation from muscarine receptors in bovine cardiac left ventricular and tracheal smooth muscle membranes were studied in the absence and presence of three muscarine antagonists. It was found that [3H]dexetimide dissociation from cardiac muscarine receptors was monophasic and very fa...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(89)90045-x
更新日期:1989-03-07 00:00:00
abstract::Airway reactivity was examined in anaesthetized guinea-pigs 18-24 h after inhalation challenge of ovalbumin-sensitized animals with ovalbumin. Bronchoconstrictor responses were measured from the increases in pulmonary inflation pressure. The study was undertaken to examine whether ovalbumin challenge induced airway hy...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00215-5
更新日期:1998-05-22 00:00:00
abstract::The correlation between the Phosphoinositide 3-kinase (PI3K) axis and crucial mechanisms involved in the maintenance of the neoplastic nature of multiple myeloma (MM) has recently evolved a general agreement that PI3K inhibition-based therapies could construct an exciting perspective for the future treatment strategie...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2018.10.036
更新日期:2019-01-05 00:00:00
abstract::The vascular response to most neurotransmitters of different vascular beds is altered under hypertensive condition. The modulatory effect of genetic pulmonary arterial hypertension on histamine responses is not known. The present study was undertaken to evaluate the modulatory effect of enzymatic degradation (via hist...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)01759-x
更新日期:2003-05-30 00:00:00
abstract::The present study investigated whether there is any difference between the effects of benzodiazepine and non-benzodiazepine anxiolytics on maternal aggression in lactating mice, using an ethological technique. We used SM-3997, a 5-HT1A receptor ligand, as a non-benzodiazepine anxiolytic. Behavior towards an intruder m...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90677-i
更新日期:1991-07-23 00:00:00
abstract::To obtain further insight into the interactions between the N-methyl-D-aspartate receptor and opioid receptor systems, we have investigated the effects of the acute treatment of morphine on the expression of serine racemase and D-amino acid oxidase mRNAs in several brain areas of rats. The morphine administration prod...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2005.09.001
更新日期:2005-11-21 00:00:00
abstract::AMN082 is a selective metabotropic glutamate mGlu7 receptor agonist reported to exhibit antidepressant activity. Considering that excessive glutamate release is involved in the pathogenesis of depression, the effect of N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082) on glutamate release in rat cerebroco...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2018.01.038
更新日期:2018-03-15 00:00:00
abstract::An in vitro method was developed for the biochemical and autoradiographic demonstration of low muscarinic receptor densities in peripheral tissue. Histological criteria point clearly to the necessity for fixation to preserve tissue quality. [3H]l-Quinuclidinylbenzilate bound specifically to a homogeneous class of bind...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90342-1
更新日期:1988-01-05 00:00:00
abstract::We previously reported that circulating lipid (malondialdehyde, MDA) and protein oxidation (carbonyl residues, CO) products can be used as markers of risk for complications in poorly controlled type 2 diabetics. Now, we aimed to evaluate the existence of a gender effect on classical disease markers and oxidative stres...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2015.09.041
更新日期:2015-11-05 00:00:00
abstract::The putative imidazoline I(3) receptor antagonist 2-(2-ethyl-2,3-dihydrobenzo[b]furan-2-yl)-1H-imidazole (KU14R) has been shown to block the effects of the atypical I(3) agonist efaroxan at the level of the ATP-sensitive K(+) (K(ATP)) channel in isolated pancreatic islet beta cells, but its effects in vivo are not kno...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)02473-1
更新日期:2002-11-01 00:00:00
abstract::Protective effects of OP-2507 [15-cis-(4-propylcyclohexyl)-16,17,18,19,20-pentanor-9-deoxy -9 alpha, 6-nitrilo-PGF1 methyl ester] against cerebral anoxia and edema were investigated in a variety of experimental models in mice and rats. OP-2507 given s.c. or p.o. led to a consistent and dose-dependent prolongation of s...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90706-5
更新日期:1986-04-29 00:00:00
abstract::We have characterized a specific binding site for angiotensin IV on bovine aortic endothelial cell membranes. Pseudo-equilibrium studies at 37 degrees C for 2 h have shown that this binding site recognizes angiotensin IV with a high affinity (Kd = 0.71; average of two experiments that yielded values of 0.71 and 0.72 n...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(95)90142-6
更新日期:1995-10-15 00:00:00
abstract::It has been well documented that nordihydroguaiaretic acid (NDGA), a phenolic lignan isolated from the creosote bush, Larrea tridentate, has anti-cancer activity in vitro and in vivo. Several mechanisms have been identified that could contribute to these actions, as NDGA directly inhibits metabolic enzymes and recepto...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2009.06.012
更新日期:2009-08-15 00:00:00
abstract::Carbamazepine, a drug effective in pain, seizure, and affective disorders, was screened for its ability to interact with a variety of neurotransmitter and neuromodulator binding sites on brain membranes. The most potent effect was observed on adenosine antagonist ( [3H]DPX) binding to the adenosine receptor (KI = 3.5 ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(83)90135-8
更新日期:1983-09-30 00:00:00
abstract::To investigate the significance of endogenous, neuroleptic-like gamma-type endorphins and their putative receptors, polyclonal and monoclonal antibodies against gamma-type endorphins, which may bio-inactivate the ligands for the receptors, and monoclonal anti-idiotype antibodies, which presumably bind to the receptors...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00157-g
更新日期:1995-06-12 00:00:00
abstract::The aim of the present study was to determine the effect of a calcium channel blocker on renal function, urinary endothelin excretion and endothelin receptor number in rats. Administration of cyclosporine resulted in a significant impairment of renal function when measured by either [14C]inulin or 24 h creatinine clea...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90132-a
更新日期:1991-02-26 00:00:00
abstract::The 235-1 pituitary tumor clone was utilized to study prolactin secretion after perturbing cyclic AMP and calcium metabolism. Cellular cyclic AMP levels were elevated after treatment with PGE1, cholera toxin, forskolin, isobutylmethylxanthine as well as dibutryl cyclic AMP; these cyclic AMP responses were associated w...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90393-0
更新日期:1985-03-12 00:00:00
abstract::Neurotensin induced the release of histamine from both purified and non-purified rat peritoneal mast cells by a non-cytotoxic mechanism. It was effective at a concentration as low as 10(-8) M. The dose-response curve for the neurotensin effect was triphasic: and initial gentle rise, a plateau (2.5 X 10(-7) -2.5 X 10(-...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90494-5
更新日期:1981-12-03 00:00:00
abstract::This study examined whether the antinociceptive activity of THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), a GABA agonist, is mediated through an action exerted at the level of the spinal cord. Intrathecal injection of doses of THIP devoid of motor effects (1-2 micrograms) did not increase tail flick or hot pl...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90197-3
更新日期:1984-08-03 00:00:00
abstract::Animal and human pharmacological studies indicate that the antipsychotic action of cyamemazine results from blockade of dopamine D(2) receptors, its anxiolytic properties from serotonin 5-HT(2C) receptor antagonism and the low incidence of extrapyramidal side effects from a potent 5-HT(2A) receptor antagonistic action...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.09.025
更新日期:2008-01-14 00:00:00
abstract::The pharmacological properties of two angiotensin II analogues containing carboranylalanine (Car) are reported. Sar-Arg-Val-Tyr-Val-His-Pro-Car is a weak partial agonist showing 15% intrinsic activity and a very long lasting action, specific for the angiotensin II receptor of the rabbit aorta. Sar-Arg-Val-Car-Val-His-...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(80)90458-6
更新日期:1980-09-05 00:00:00
abstract::Histone deacetylases (HDACs) can regulate cancer progression and its inhibitors (HDACIs) have been widely used for cancer therapy. Valproic acid (VPA, 2-propylpentanoic acid) can inhibit the class I HDAC and suppress the malignancy of solid cancers. Our present study revealed that 1 mM VPA, which has no effect on cell...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.172745
更新日期:2019-12-15 00:00:00
abstract::The purpose of our study was to determine whether a toxic arrhythmogenic dose of digitalis administered to an in vivo preparation would affect the neuronal uptake of norepinephrine, serotonin and dopamine in brain tissue and norepinephrine in cardiac tissue. This was investigated by intoxicating anesthetized cats with...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(78)90020-1
更新日期:1978-11-01 00:00:00
abstract::Some reports published from 1967 to 1999 describe the use of ointments containing high doses (0.1 to 0.2%, w/w) C. asiataica herb extracts to enhance wound repair. Lower doses at which burn wound repair is enhanced by such topical applications have not been established yet. We found that the application of asiaticosid...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.02.036
更新日期:2008-04-28 00:00:00
abstract::C-type natriuretic peptide (CNP) is the major natriuretic peptide in the brain and its mRNA has been reported in the central nervous system, which supports local synthesis and its role as a neuromodulator. The aim of the present work was to study the effect of centrally applied CNP on pancreatic secretion. Rats were f...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2005.09.015
更新日期:2005-11-07 00:00:00
abstract::Acute leukemia is a malignant clonal hematopoietic stem cell disease. In the current study, we examined the effects of bryostatin 5 on acute monocytic leukemia cells in vitro and in vivo. We also explored the mechanisms and pathways underlying the increase in apoptosis induced by bryostatin 5. Bryostatin 5 inhibited t...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2013.08.012
更新日期:2013-10-15 00:00:00