Abstract
Propoxyphene and its principal metabolite, norpropoxyphene, depressed maximum developed isometric tension (T) and its first derivative, dT/dt, in isolated cat right ventricular papillary muscles. T and dT/dt were reduced by 10-5 M concentrations of each drug (p<0.005), and this effect was markedly intensified at 10-4 M: propoxyphene, 49% reduction of T (p<0.001); norpropoxyphene, 36% reduction of T (p<0.001). Nonresponsiveness to electrical stimulation developed in the majority of muscles at the 10-5 M concentration of each drug and in all muscles at 10-4 M. The cardiac depressant actions of the two drugs administered simultaneously at a concentration of 10-5 M each were additive, resulting in a 15.6% decline in T. The contractile actions of propoxyphene and norpropoxyphene were not altered by the specific narcotic blocking agent, naloxone, indicating these effects were produced by a nonopiate mechanism. In contrast to propoxyphene and norpropoxyphene, morphine produced no reductions in T or dT/dt at a concentration of 10-5 M and only a slight, albeit significant (p<0.05), depression of T (-4%) and dT/dt (-6%) at 10-4 M. The cardiac depressant effects of propoxyphene and norpropoxyphene were at least partially reversible, as indicated by substantial recovery of contractile function after drug removal (to 69-75% of control T) and by a positive inotropic response to isoproterenol. These results indicate that at high concentrations propoxyphene and norpropoxyphene have a cardiac depressant action characterized by decreased electrical excitability and reversible contractile depression, effects which are consistent with a local anesthetic action. Depression of cardiac contractile and electrophysiologic functions by propoxyphene and norpropoxyphene may play a role in the clinical toxicity associated with propoxyphene overdose.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 129-138 |
| Number of pages | 10 |
| Journal | Journal of Cardiovascular Pharmacology |
| Volume | 3 |
| Issue number | 1 |
| State | Published - 1981 |
Fingerprint
ASJC Scopus subject areas
- Pharmacology
- Cardiology and Cardiovascular Medicine
Cite this
Depression of myocardial contractile function by propoxyphene and norpropoxyphene. / Amsterdam, Ezra A; Rendig, S. V.; Henderson, G. L.; Mason, D. T.
In: Journal of Cardiovascular Pharmacology, Vol. 3, No. 1, 1981, p. 129-138.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Depression of myocardial contractile function by propoxyphene and norpropoxyphene
AU - Amsterdam, Ezra A
AU - Rendig, S. V.
AU - Henderson, G. L.
AU - Mason, D. T.
PY - 1981
Y1 - 1981
N2 - Propoxyphene and its principal metabolite, norpropoxyphene, depressed maximum developed isometric tension (T) and its first derivative, dT/dt, in isolated cat right ventricular papillary muscles. T and dT/dt were reduced by 10-5 M concentrations of each drug (p<0.005), and this effect was markedly intensified at 10-4 M: propoxyphene, 49% reduction of T (p<0.001); norpropoxyphene, 36% reduction of T (p<0.001). Nonresponsiveness to electrical stimulation developed in the majority of muscles at the 10-5 M concentration of each drug and in all muscles at 10-4 M. The cardiac depressant actions of the two drugs administered simultaneously at a concentration of 10-5 M each were additive, resulting in a 15.6% decline in T. The contractile actions of propoxyphene and norpropoxyphene were not altered by the specific narcotic blocking agent, naloxone, indicating these effects were produced by a nonopiate mechanism. In contrast to propoxyphene and norpropoxyphene, morphine produced no reductions in T or dT/dt at a concentration of 10-5 M and only a slight, albeit significant (p<0.05), depression of T (-4%) and dT/dt (-6%) at 10-4 M. The cardiac depressant effects of propoxyphene and norpropoxyphene were at least partially reversible, as indicated by substantial recovery of contractile function after drug removal (to 69-75% of control T) and by a positive inotropic response to isoproterenol. These results indicate that at high concentrations propoxyphene and norpropoxyphene have a cardiac depressant action characterized by decreased electrical excitability and reversible contractile depression, effects which are consistent with a local anesthetic action. Depression of cardiac contractile and electrophysiologic functions by propoxyphene and norpropoxyphene may play a role in the clinical toxicity associated with propoxyphene overdose.
AB - Propoxyphene and its principal metabolite, norpropoxyphene, depressed maximum developed isometric tension (T) and its first derivative, dT/dt, in isolated cat right ventricular papillary muscles. T and dT/dt were reduced by 10-5 M concentrations of each drug (p<0.005), and this effect was markedly intensified at 10-4 M: propoxyphene, 49% reduction of T (p<0.001); norpropoxyphene, 36% reduction of T (p<0.001). Nonresponsiveness to electrical stimulation developed in the majority of muscles at the 10-5 M concentration of each drug and in all muscles at 10-4 M. The cardiac depressant actions of the two drugs administered simultaneously at a concentration of 10-5 M each were additive, resulting in a 15.6% decline in T. The contractile actions of propoxyphene and norpropoxyphene were not altered by the specific narcotic blocking agent, naloxone, indicating these effects were produced by a nonopiate mechanism. In contrast to propoxyphene and norpropoxyphene, morphine produced no reductions in T or dT/dt at a concentration of 10-5 M and only a slight, albeit significant (p<0.05), depression of T (-4%) and dT/dt (-6%) at 10-4 M. The cardiac depressant effects of propoxyphene and norpropoxyphene were at least partially reversible, as indicated by substantial recovery of contractile function after drug removal (to 69-75% of control T) and by a positive inotropic response to isoproterenol. These results indicate that at high concentrations propoxyphene and norpropoxyphene have a cardiac depressant action characterized by decreased electrical excitability and reversible contractile depression, effects which are consistent with a local anesthetic action. Depression of cardiac contractile and electrophysiologic functions by propoxyphene and norpropoxyphene may play a role in the clinical toxicity associated with propoxyphene overdose.
UR - http://www.scopus.com/inward/record.url?scp=0019372168&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0019372168&partnerID=8YFLogxK
M3 - Article
C2 - 6160342
AN - SCOPUS:0019372168
VL - 3
SP - 129
EP - 138
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 1
ER -