Abstract：
:1. The three dimensional requirements for inhibition of ACE (angiotensin converting enzyme) were investigated in order to facilitate design of a more potent and selective antihypertensive agent. 2. All compounds designed possessed a bicyclic unit incorporating carboxylate and amidic carbonyl groups together with a thiol-bearing side chain. 3. NMR spectroscopy of the bicyclic units and molecular mechanics calculations enabled the possible positions of the thiol group to be studied. 4. Determination of the positions of the thiol group conferring best inhibition in the active site of ACE permitted the probable location of the active site zinc ion to be identified. The intention was to replace the thiol side chain with a homophenylalanine unit to bind to the zinc ion and also to occupy the S1 site which fits the Phe8 side chain of angiotensin I. 5. Examination of a torsional angle psi in a compound possessing poor inhibitory potency indicated correspondence to a high energy conformation of alanylproline. The bicyclic unit was modified to incorporate a seven-instead of a six-membered ring to bring psi into the range of an accessible conformation of alanylproline. The corresponding IC50 resulting indicated that psi was closer to that of the active conformations of enalaprilat and captopril. 6. Removal of one carbonyl improved the ACE inhibitory potency further. 7. The postulated active conformation of cilazaprilat is presented.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Attwood MRdoi
10.1111/j.1365-2125.1989.tb03474.xsubject
Has Abstractpub_date
1989-01-01 00:00:00pages
133S-137Seissn
0306-5251issn
1365-2125journal_volume
27 Suppl 2pub_type
杂志文章abstract：:Caffeine (5 mg kg-1) was administered orally to two healthy, non-smoking subjects on three separate occasions--before, and during therapy with the xanthine oxidase inhibitor allopurinol at doses of either 300 or 600 mg daily. Plasma and urinary levels of methylxanthines, endogenous oxypurines and allopurinol and its m...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1986.tb05222.x
更新日期：1986-04-01 00:00:00
abstract：AIMS:To estimate the rates of common adverse events in patients treated with the proton pump inhibitors omeprazole, lansoprazole and pantoprazole in general practice in England. METHODS:In prescription-event monitoring cohort studies, data on dispensed prescriptions prescribed by general practitioners in England soon ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2000.00262.x
更新日期：2000-10-01 00:00:00
abstract：:1 Two studies were carried out on acutely psychotic patients receiving chlorpromazine (100 mg) 8-hourly. 2 In the pilot study on five patients, plasma chlorpromazine concentrations fell over the course of 3 weeks of treatment and parallel changes were noted in the plasma half-life of antipyrine, salivation rate and ha...
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.1365-2125.1975.tb01576.x
更新日期：1975-06-01 00:00:00
abstract：AIMS:Carbamazepine (CBZ) is an inducer of cytochrome P450 enzymes, which have been implicated in many drug interactions. However, for immunosuppressant and anti-HIV drugs, whose main site of action is the lymphocyte, induction of P-glycoprotein (Pgp) may also be important. In this study, we have investigated whether CB...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2006.02587.x
更新日期：2006-08-01 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：AIMS:The aims of this study were to determine the effects of the nonsteroidal, selective aromatase inhibitor, anastrozole, at steady-state concentrations, on the pharmacokinetics and pharmacodynamics of warfarin, and to assess whether or not anastrozole alone has any anticoagulant activity. METHODS:This was a randomiz...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1365-2125.2001.01358.x
更新日期：2001-05-01 00:00:00
abstract：INTRODUCTION:Irrational medicine use is a global crisis, but incidences are proportionately higher in low and middle-income countries like Sierra Leone. This study explores the structure, functions, and challenges of Drug and Therapeutics Committees (DTC) an intervention towards irrational medicines use recently pilote...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.14716
更新日期：2021-01-04 00:00:00
abstract：:Responses of human bronchial strip preparations to contractile and relaxant agonists were measured in preparations from non-diseased and from asthmatic lung obtained 3-15 h post-mortem. The potencies of carbachol and histamine were approximately two times less in asthmatic than in non-diseased bronchi. This was statis...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1986.tb02956.x
更新日期：1986-12-01 00:00:00
abstract：:A free lignocaine index was developed on the basis of measurements of plasma lignocaine and its principle binding protein, alpha 1-acid glycoprotein (AAG) in 80 samples from 16 patients admitted to the coronary care unit and given prophylactic lignocaine therapy. The free drug fraction, fu, of lignocaine was determine...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb05132.x
更新日期：1985-12-01 00:00:00
abstract：AIMS:To develop a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP)-based assay to genotype for hepatic CYP3A5 expression and to use this assay to study a British population. METHODS:CYP3A5-specific primers were designed with one including a base-pair mismatch to create a RsaI site in sam...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2003.01798.x
更新日期：2003-06-01 00:00:00
abstract：AIMS:This double-blind, randomized, four-period, two-way crossover study was conducted to evaluate the acute effects of oral sildenafil (100-mg single dose) on sperm motility, count, density, morphology and vitality as well as ejaculate volume and viscosity in healthy male subjects. The concentrations of sildenafil and...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.0306-5251.2001.00033.x
更新日期：2002-01-01 00:00:00
abstract：:The deployment of artesunate for severe malaria and the artemisinin combination therapies (ACTs) for uncomplicated malaria has been a major advance in antimalarial therapeutics. These drugs have reduced treated mortality, accelerated recovery and reduced treatment failure rates and transmission from the treated infect...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.14474
更新日期：2020-07-12 00:00:00
abstract：BACKGROUND AND PURPOSE:Develop a translational assay of Transient Receptor Potential Ankyrin 1 (TRPA1) activity for use as a preclinical and clinical biomarker. EXPERIMENTAL APPROACH:Allyl isothiocyanate (AITC), capsaicin or citric acid were applied to ears of wildtype and Trpa1-knock out (Trpa1 KO) rats, and changes ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14370
更新日期：2021-01-01 00:00:00
abstract：:1. The antitussive properties of bronchodilators were evaluated in a total of 47 normal volunteers. 2. Cough was induced by inhalation of ultrasonically nebulized solutions of distilled water and hypotonic saline. 3. Inhaled fenoterol hydrobromide (360 micrograms; 20 volunteers) and inhaled ipratropium bromide (72 mic...
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.1365-2125.1987.tb03204.x
更新日期：1987-10-01 00:00:00
abstract：:1. The attitudes of general practitioners and hospital physicians to the management of hypertension in the elderly, were examined by responses to a postal questionnaire distributed within the Northern Region, concerning the management of a healthy 75 year old male non-smoker with sustained diastolic or isolated systol...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1995.tb04481.x
更新日期：1995-05-01 00:00:00
abstract：AIMS:To examine the feasibility of using the human iris in vivo for the assessment of the interaction between tyramine and monoamine oxidase (MAO) inhibitors. To examine the relative roles of the two forms of MAO in terminating the response to sympathomimetic amines in the iris, by comparing the effects of single oral ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1365-2125.1998.00729.x
更新日期：1998-06-01 00:00:00
abstract：AIMS:To assess the prevalence of potentially inappropriate medications (PIMs) use in a population of community-based multicompartment compliance aid (MCA) users in north-east Scotland. METHODS:Data for MCAs dispensed by 48 of the 50 community pharmacies in Aberdeen City between 1st June to 31st October 2014, together ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13220
更新日期：2017-07-01 00:00:00
abstract：AIMS:Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon but potentially debilitating condition, characterised by nonhealing jawbone, with or without mucosal exposure, in the presence of certain drugs. Those already strongly associated with MRONJ include antiresorptives denosumab and bisphosphonates; how...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14681
更新日期：2020-11-27 00:00:00
abstract：:1. Medication errors are common in general practice and in hospitals. Both errors in the act of writing (prescription errors) and prescribing faults due to erroneous medical decisions can result in harm to patients. 2. Any step in the prescribing process can generate errors. Slips, lapses, or mistakes are sources of e...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2009.03425.x
更新日期：2009-06-01 00:00:00
abstract：AIMS:Hypertension is a common comorbidity of patients with COVID-19, SARS or HIV infection. Such patients are often concomitantly treated with antiviral and antihypertensive agents, including ritonavir and nifedipine. Since ritonavir is a strong inhibitor of CYP3A and nifedipine is mainly metabolized via CYP3A, the com...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14684
更新日期：2020-12-02 00:00:00
abstract：:1. The effects of heart failure due to chronic myocardial infarction on the responsiveness to injected angiotensin I and ACE inhibition by intravenous cilazapril (1 mg kg-1) were evaluated. 2. For this purpose one group of 17 rats with a 4-week old myocardial infarction was compared with a group of 10 sham operated ra...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb03478.x
更新日期：1989-01-01 00:00:00
abstract：AIMS:Graft spasm may develop during coronary artery bypass grafting and reversal of spasm is still challenging. The purpose of this study was to investigate the in vitro vascular relaxant properties of AJ-2615 in human internal mammary artery (IMA). METHODS:We studied 264 IMA rings taken from 65 patients undergoing co...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.0306-5251.2001.01444.x
更新日期：2001-09-01 00:00:00
abstract：AIMS:Clozapine (CLZ), an atypical neuroleptic with a high risk of causing agranulocytosis, is metabolized in the liver to desmethylclozapine (DCLZ) and clozapine N-oxide (CLZ-NO). This study investigated the involvement of different CYP isoforms in the formation of these two metabolites. METHODS:Human liver microsomal...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1997.t01-1-00605.x
更新日期：1997-11-01 00:00:00
abstract：:The current U.K. trial protocol (UKALL XI) for childhood lymphoblastic leukaemia demands mercaptopurine (MP) dose escalation in children who tolerate daily 75 mg/m2 MP (100% dose) without cytopenias. The previous trial (UKALL X) did not. MP metabolism was studied in a group of UKALL XI children (n = 21) who tolerated ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1996.44921.x
更新日期：1996-10-01 00:00:00
abstract：:1 The effects of propranolol and atenolol given in random order in a cross-over study to fifteen patients with essential hypertension have been studied. 2 Both drugs were effective in lowering blood pressure and side effects were not markedly different. 3 There was no change in exchangeable sodium or potassium or in t...
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.1365-2125.1980.tb00501.x
更新日期：1980-07-01 00:00:00
abstract：:In a double-blind crossover trial, the effect of 4 week daily ingestion of eight cups of regular coffee (corresponding to 504 mg caffeine) vs eight cups of decaffeinated coffee was studied. Blood pressure, heart rate and urinary catecholamines were measured in eight healthy, young volunteers. In both groups, regular 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.1365-2125.1983.tb01553.x
更新日期：1983-06-01 00:00:00
abstract：AIMS:To investigate uptake of fluconazole into the interstitial fluid of human subcutaneous tissue using the microdialysis and suction blister techniques. METHODS:A sterile microdialysis probe (CMA/60) was inserted subcutaneously into the upper arm of five healthy volunteers following an overnight fast. Blisters were ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2003.01930.x
更新日期：2003-11-01 00:00:00
abstract：:Clinical pharmacologists are the only medical specialists whose training focuses specifically on the safe, effective and cost-effective use of medicines, underpinned by an understanding of drug discovery, drug regulation, pharmacology, translational medicine and the performance of clinical trials. This unique perspect...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2012.04244.x
更新日期：2012-06-01 00:00:00
abstract：:1. Recent work has demonstrated artificial penile erection after intracavernous injection of prostaglandin E1 (PGE1). A possible dose-response relationship between PGE1 and its erectile action was examined in a double-blind, cross-over designed, placebo-controlled study. 2. Twenty patients aged (mean +/- s.d.) 45 +/- ...
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.1365-2125.1989.tb03543.x
更新日期：1989-11-01 00:00:00
abstract：:The coming of age of molecular biology has resulted in an explosion in our understanding of the pathogenesis of virus related diseases. New pathogens have been identified and characterized as being responsible for old diseases. Empirical clinical evaluation of morbidity and mortality as outcome measures after a therap...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1046/j.1365-2125.2002.01623.x
更新日期：2002-07-01 00:00:00
