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A sequential model of pharmacologic assays for evaluating myocardial depressant effects of potential cardiovascular drugs
Author(s) -
Kitzen Jan M.,
Schwenkler Mary A.,
Moeller Janice E.,
Novick William J.
Publication year - 1982
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430020309
Subject(s) - verapamil , hydralazine , depressant , clonidine , pharmacology , hemodynamics , medicine , anesthesia , blood pressure , calcium
A model of sequentially arranged pharmacologic assays was developed to evaluate myocardial‐depressant properties of various drugs. The sequence of assays consisted of the following: hemodynamics in normal dogs, hemodynamics in ganglion‐blocked dogs, isolated‐stimulated guinea pig left atria, spontaneously beating guinea pig atria, and an optional follow‐up experiment consisting of hemodynamics in ganglion‐blocked dogs with cardiac pacing. Four reference compounds (clonidine, verapamil, hydralazine, and mixidine) plus a test compound (P79‐4058) were subjected to the test model with the goal of being able to discriminate between various types of myocardial depression. Results from this study indicate that the model was able to separate out three classes of actions: drugs with no depressant activity (hydralazine), drugs that cause myocardial depression indirectly via the nervous system (clonidine), and a third group that elicit myocardial depression directly (verapamil and P79‐4058). Mixidine produced variable results in this model. The proposed model appeared to be adequate in that enough information can be obtained so that new pharmacologic compounds may be evaluated and decisions as to further development can be made.