Premium
The cardiovascular actions of WR‐149,024 (1,18‐diamino‐7,13‐diaza‐9,10‐dithiaoctadecane tetrahydrochloride)
Author(s) -
CALDWELL R. W.,
HEIFFER M. H.,
HERMAN E. H.
Publication year - 1972
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1972.tb06889.x
Subject(s) - phenylephrine , heart rate , blood pressure , bradycardia , medicine , isoprenaline , blockade , anesthesia , angiotensin ii , chemistry , baroreflex , endocrinology , stimulation , receptor
Summary1 . The general cardiovascular properties of WR‐149,024 (a straight chain sulphur‐containing aliphatic amine) in dogs and cats are reported. 2 . Intravenous administration of this compound produced an immediate hypotension and bradycardia in intact anaesthetized dogs. These effects were independent of the parasympathetic nervous system since they were also present in atropinized and bilaterally vagotomized dogs. 3 . Ascending aortic blood flow increased after administration of WR‐149,024 despite a reduction in blood pressure, contractile force and heart rate. It appears that the initial hypotension is due to a decrease in total peripheral vascular resistance since WR‐149,024 produced relatively little change in force of contraction or heart rate in the isolated, blood‐perfused heart preparation. 4 . WR‐149,024 reversed the pressor effects of adrenaline within 10 min of injection while at the same time the vasopressor response to angiotensin or the vasodepressor response to isoprenaline was not altered. α‐Adrenoceptor blockade was still evident up to five days after dosing. 5 . WR‐149,024 did not block phenylephrine inhibition of intestinal motility. These findings suggest that WR‐149,024 initiates a relatively specific and prolonged α‐adrenoceptor blockade.