Abstract:
:1. Effects of 3 h infusions of adrenaline (0.4 nmol kg-1 min-1) or placebo and of mental stress evoked by a colour word test (CWT) on adrenergic receptor function were investigated in healthy men. Responses of heart rate, blood pressure, plasma catecholamines, plasma cyclic AMP and plasma free fatty acids (FFA) were evaluated during infusions and CWT. In vitro beta 2-adrenoceptor numbers [( 125I]-HYP binding) and function (isoprenaline induced cyclic AMP accumulation) were studied on lymphocytes in all experiments. alpha 2-adrenoceptor binding [( 3H]-yohimbine and adrenaline) to intact platelets was evaluated in the infusion experiments only. 2. Placebo infusion evoked no major alterations of any parameter. 3. Adrenaline infusion raised venous plasma adrenaline levels to 4-5 nmol l-1, increased heart rate by 14 +/- 3 beats min-1 and plasma cyclic AMP by 17 +/- 3 nmol l-1, and decreased diastolic blood pressure by 15 +/- 5 mm Hg. These responses persisted throughout the infusion. Plasma FFA levels, on the other hand, increased at 30 min of infusion (from 236 +/- 44 to 717 +/- 92 mumol l-1) and returned to basal levels after 3 h of infusion. 4. In vitro, lymphocytes showed increased beta 2-responsiveness after 30 min of adrenaline infusion (delta cyclic AMP increased from 1.86 +/- 0.24 to 3.06 +/- 0.58 pmol/10(6) cells), but a decreased response (0.47 +/- 0.10 pmol/10(6) cells) after 3 h of infusion. [125I]-HYP binding to lymphocyte membranes showed a three-fold increase of Bmax at 30 min of adrenaline infusion followed by a return to basal values after 3 h of infusion. [125I]-HYP binding reflected the functional responsiveness of the lymphocytes in vitro poorly. alpha 2-adrenoceptors on platelets were not altered with regard to Bmax or Kd for [3H]-yohimbine binding or Ki for adrenaline displacement of [3H]-yohimbine binding. 5. CWT evoked marked circulatory changes, a four-fold increase in plasma adrenaline and a 60% increase in beta 2-adrenoceptor binding sites without changes in functional responsiveness of the lymphocytes. 6. We conclude that exposure to high physiological levels of adrenaline in vivo alters lymphocyte beta-adrenoceptor responsiveness in a biphasic manner, with an early increase followed by a later decrease, but that most beta-adrenoceptor mediated responses to adrenaline in vivo remain intact. Lymphocyte alterations may reflect recruitment of cells into the circulation during sympathoadrenal stimulation. Platelet alpha 2-adrenoceptors are apparently not easily subjected to agonist induced dynamic receptor regulation.(ABSTRACT TRUNCATED AT 400 WORDS)
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Larsson PT,Martinsson A,Olsson G,Hjemdahl Pdoi
10.1111/j.1365-2125.1989.tb03559.xsubject
Has Abstractpub_date
1989-12-01 00:00:00pages
663-74issue
6eissn
0306-5251issn
1365-2125journal_volume
28pub_type
临床试验,杂志文章abstract::1. Eight volunteers received in randomized order two 30 microliters drops of either 1% w/v cyclopentolate hydrochloride or a corresponding amount of cyclopentolate polygalacturonate in saline or in acetate buffer in one eye. Cyclopentolate concentrations in plasma were measured by a radioreceptor assay. 2. Peak plasma...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1993.tb04173.x
更新日期:1993-05-01 00:00:00
abstract::WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Dihydropyrimidine dehydrogenase (DPD) is the enzyme responsible for the elimination of approximately 80% of the administered dose of 5-fluorouracil (5-FU). * Mutations in the DPD-coding gene have been shown to increase the risk of severe toxicity in 5-FU treated patients. * T...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03683.x
更新日期:2010-08-01 00:00:00
abstract:AIMS:Establishing a pharmacological challenge model could yield an important tool to understand the complex role of the nicotinic cholinergic system in cognition and to develop novel compounds acting on the nicotinic acetylcholine receptor. METHODS:This randomized, double-blind, double-dummy, placebo-controlled, four-...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.13507
更新日期:2018-05-01 00:00:00
abstract:AIMS:To determine role of CYP2D6 activity in the pharmacokinetics of propafenone (PPF) enantiomers in native Chinese subjects. METHODS:Sixteen extensive metabolizers (EMs) and one poor metabolizer (PM), whose phenotype had been previously assessed with dextromethorphan metabolic phenotyping, were enrolled. Blood sampl...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.1999.00932.x
更新日期:1999-05-01 00:00:00
abstract::Medroxalol, a new drug which has been reported to possess both alpha- and beta-adrenoceptor antagonist properties, was compared with labetalol in single dose studies in normotensive males. Oral doses of 400 mg of each drug significantly reduced blood pressure, both supine and erect, without significant changes in hear...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02391.x
更新日期:1984-05-01 00:00:00
abstract::Plasma concentrations of isoniazid and N-acetylisoniazid were measured at varying times after addition of both compounds to plasma (5 micrograms/ml) and storage at several different temperatures (-70 degrees C, -20 degrees C, 4 degrees C and 20 degrees C). The concentration of both compounds declined log-linearly with...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb01496.x
更新日期:1983-02-01 00:00:00
abstract::The effects of separate 7 day pretreatments with sulphinpyrazone (800 mg daily) and cimetidine (1 g daily) on the disposition of (+/-)-verapamil have been examined in eight healthy volunteers (four male, four female). Each subject received single oral (80 mg) and intravenous (0.15 mg/kg) doses of verapamil on differen...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02658.x
更新日期:1985-03-01 00:00:00
abstract::Little is known about the administration of direct-acting oral anticoagulants (DOACs) and the occurrence of alopecia. Our aim was to analyse the reports of alopecia following DOAC administration received until 2 May 2018 from VigiBase, the World Health Organization database. A descriptive analysis of age, sex, serious...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14221
更新日期:2020-08-01 00:00:00
abstract::The effects of single doses of anhydrous caffeine (250 mg and 500 mg) and placebo on physiological, psychological measures and subjective feelings were studied in a double-blind, cross-over study in nine healthy subjects who had abstained from caffeine-containing beverages for 24 h before each occasion. Caffeine and c...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1986.tb02883.x
更新日期:1986-07-01 00:00:00
abstract::A double-blind, crossover study was carried out on the acceptability of three doses of brotizolam (0.125, 0.25 and 0.5 mg) in chronic insomniacs aged between 21 and 75 years (33 men: 42 women). Patients reported a shorter time to fall asleep and less nocturnal awakenings. Improvement in sleep was evident during the fi...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1983.tb02319.x
更新日期:1983-01-01 00:00:00
abstract::The fall in blood pressure produced by captopril is not accompanied by a compensatory tachycardia. Angiotensin converting enzyme may participate in the metabolism of endogenous opioids and these substances can lower blood pressure without reflex tachycardia. It is therefore possible that the hypotensive effect of capt...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1984.tb02408.x
更新日期:1984-06-01 00:00:00
abstract:AIMS:The cytochrome P450 enzyme CYP2C9 catalyses the 4'-hydroxylation of the nonsteroidal analgesic drug diclofenac in humans. We studied the influences of the known amino acid variants, CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu), on diclofenac pharmacokinetics after a 50-mg oral dose of diclofenac in healthy volunt...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.01712.x
更新日期:2003-01-01 00:00:00
abstract:AIMS:The main goal of the study was to describe the pharmacokinetics of maternal zidovudine (ZDV) administration during pregnancy and labour and to evaluate their impact on fetal concentrations and exposures. METHODS:A total of 195 HIV-infected pregnant and non-pregnant women aged 16-59 years were included and 273 mat...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12459
更新日期:2014-12-01 00:00:00
abstract:AIMS:To investigate impacts of withdrawal and regulatory advice regarding cyclooxygenase-2 (COX-2) inhibitors on UK population rates of gastrointestinal haemorrhage and acute myocardial infarction (MI). METHODS:Ecological time series study of prescribing, mortality and hospital admission trends in people aged > or = 5...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2009.03500.x
更新日期:2009-11-01 00:00:00
abstract:AIM:Sunitinib is an oral tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). Because of the large interpatient pharmacokinetic variability and established exposure-response and exposure-toxicity relationships in clinical trial patients, therapeut...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14332
更新日期:2020-05-01 00:00:00
abstract::A double-blind controlled study comparing the effects of intravenous Diazemuls (0.15 mg kg-1) with midazolam (0.07 mg kg-1) in patients with normal liver function and with cirrhosis and portal hypertension is described. The clinical effect of the two drugs was assessed by serial tests of psychomotor function before an...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1986.tb02952.x
更新日期:1986-12-01 00:00:00
abstract::Since platelet activation has been incriminated in the pathogenesis of asthma, we have investigated the effect of one of its major granule-derived mediators, 5-hydroxytryptamine (5-HT, serotonin) on airway calibre in normal (12), atopic non-asthmatic (12) and atopic asthmatic subjects (16). On separate days subjects i...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1986.tb02923.x
更新日期:1986-10-01 00:00:00
abstract::When using biopsy pathology in clinical pharmacology to assess drug efficacy in the gastrointestinal tract, a number of questions must be answered: Is the biopsy necessary or more effective than macroscopic views by endoscopy? Can we extract maximal information from the specimen? Are there surrogate serum or other mar...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2125.2003.01981.x
更新日期:2003-11-01 00:00:00
abstract::Metabolomics is recognized as a powerful top-down system biological approach to understand genetic-environment-health paradigms paving new avenues to identify clinically relevant biomarkers. It is nowadays commonly used in clinical applications shedding new light on physiological regulatory processes of complex mammal...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2012.04216.x
更新日期:2013-03-01 00:00:00
abstract::1 The absorption of effervescent aspirin was studied in normal volunteers of both sexes under varied conditions of activity in both fasting and non-fasting states. 2 Moderate activity resulted in no significant changes in absorption compared with that at rest. 3 In non-fasting subjects the absorption was reduced but t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1974.tb00222.x
更新日期:1974-04-01 00:00:00
abstract:AIMS:To explore longitudinal changes in the number and type of medicines used among older people who experience polypharmacy. METHODS:We used pharmaceutical claims for a 10% sample of Australian Pharmaceutical Benefits Scheme beneficiaries to identify people aged 70 years and older who were exposed to 5 or more medici...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14504
更新日期:2020-07-31 00:00:00
abstract::The importance of number of tablets for patient compliance was investigated in 160 patients with mild-moderate essential hypertension treated with a beta-adrenoceptor blocker and a thiazide diuretic. Mean BP at entry 146 +/- 16/92 +/- 8 mm Hg. All patients were given pindolol 10 mg and clopamide 5 mg in one combinatio...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1984.tb02388.x
更新日期:1984-05-01 00:00:00
abstract::1. We report a method for measuring the concentrations of haloperidol (HL) and its major active metabolite, reduced haloperidol (RHL), in human scalp hair. 2. Hair samples were obtained from 59 patients who had been taking HL at fixed daily doses for more than 4 months and whose compliance was good. A morning pre-dose...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03618.x
更新日期:1990-02-01 00:00:00
abstract::The antiarrhythmic effects of verapamil were observed before it was appreciated that it was a calcium ion-antagonist. Intravenous verapamil is highly effective in the termination of paroxysmal reciprocating atrioventricular tachycardia, whether associated with preexcitation or involving the atrioventricular node alone...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1986.tb02869.x
更新日期:1986-01-01 00:00:00
abstract:AIMS:The aim was to describe the utilization of antidiabetic agents, in terms of persistence and regimen change, in the management of a cohort of newly treated type 2 diabetes patients and to investigate associated socio-demographic and treatment factors. METHODS:A population-based retrospective cohort study was condu...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12573
更新日期:2015-06-01 00:00:00
abstract::1. The elimination of antipyrine was investigated before and after intravenous administration of haem arginate (3 mg haem kg-1 day-1 on three or four successive days) to six patients with variegate porphyria in remission. 2. Haem arginate decreased the faecal content of protoporphyrin from 557 +/- 91 to 118 +/- 32 (me...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb05315.x
更新日期:1988-12-01 00:00:00
abstract::1 Fourteen hypertensive patients were studied by intra-arterial BP monitoring to quantify the effects of standardized physiological stresses: Valsalva manoeuvre, isometric, treadmill and bicycle exercise, and 60 degree tilting before and after labetalol treatment. 2 The dose of labetalol ranged from 100--600 mg three ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::1. A double-blind, four period crossover study was undertaken to test for an interaction between single oral doses of nifedipine retard (20 mg) and lisinopril (20 mg) in normal subjects. 2. Side effects with both drugs were mild and the incidence was additive. 3. Blood pressure (BP) was lowered by nifedipine for 4 h, ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1988.tb03308.x
更新日期:1988-03-01 00:00:00
abstract:AIMS:Drug disposition in children may vary from adults due to age-related variation in drug metabolism. Microdose studies present an innovation to study pharmacokinetics (PK) in paediatrics; however, they should be used only when the PK is dose linear. We aimed to assess dose linearity of a [14 C]midazolam microdose, b...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/bcp.14047
更新日期:2019-10-01 00:00:00
abstract::The dose-response effects of oral nicardipine on the systemic blood pressure were examined in 54 patients with uncomplicated essential hypertension (DBP greater than or equal to 100 mm Hg). The study was designed in four sequential stages. A 2 week single-blind placebo run-in period was followed by dose titration with...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1985.tb05156.x
更新日期:1985-01-01 00:00:00