Linked Life Data

3007897

Source:http://linkedlifedata.com/resource/pubmed/id/3007897

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1986-5-7
pubmed:abstractText
The aim of the present study was to establish equieffective doses of propranolol (PROP) and bufuralol (BUF) in man. Both drugs compete for radioligand binding of 3H-CGP 12177 at beta-adrenoceptors of rat reticulocytes with Ki-values of 6.7 (PROP) and 19.6 (BUF) ng/plasma in the mean. In contrast to PROP, which is a pure antagonist, BUF shows partial agonism with an intrinsic activity around 5% (relative to isoprenaline) in vitro. After i.v. injection of cumulative doses of both drugs to 10 healthy volunteers, drug present in plasma occupies beta-adrenoceptors in vitro in a dose-dependent manner up to 80%. In man the full beta-adrenoceptor agonist isoprenaline (8 micrograms/min for 3 min) induces an increase in heart rate by 73%, an increase in stroke volume by 47%, a decrease in total peripheral resistance by 63% and a shortening of the preejection period by 70%. PROP exerts effects in man in the opposite direction of isoprenaline (at resting state), whereas BUF does not influence heart rate and stroke volume to a significant extent. Only the preejection period and total peripheral resistance are influenced in analogy to the isoprenaline effects. A direct comparison of the effects of PROP and BUF at 50% in vitro receptor occupancy by the respective plasma samples shows the clear-cut qualitative differences between the pharmacodynamics of both drugs in man as expected from the comparison of the full agonist isoprenaline and the antagonist propranolol. It is concluded that only on the basis of the respective receptor occupancy one may delineate pharmacodynamic differences of different drugs of the same class in man.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0379-0355
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
645-51
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
In vitro receptor occupancy allows to establish equieffective doses of beta-blockers with different pharmacodynamic profiles in man. Investigations with propranolol and bufuralol.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't