Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Donnerer, J; Stark, U; Tritthart, HA; Lembeck, F.
CP-96,345, a non-peptide antagonist of substance P. III. Cardiovascular effects in mammals unrelated to actions on substance P receptors.
Naunyn Schmiedebergs Arch Pharmacol. 1992; 346(3):328-332
Doi: 10.1007%2FBF00173547
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- Führende Autor*innen der Med Uni Graz
- Donnerer Josef
- Co-Autor*innen der Med Uni Graz
- Lembeck Fred
- Tritthart Helmut
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- Abstract:
- The cardiovascular effects of CP-96,345, a non-peptide antagonist of substance P, were analyzed in vivo and in vitro. In the anaesthetized rat, the i.v. injection of 3 mumol kg-1 of CP-96,345 induced a fall in mean arterial blood pressure and a reduction in heart rate. Similar effects were obtained with the enantiomer CP-96,344 (2R,3R)-cis-isomer of CP-96,345) which does not interact with substance P receptors. Both enantiomers, at a concentration of 10 microM, decreased the beating frequency of the isolated atria and of the isolated perfused heart of the guinea-pig to a similar extent, and caused transient coronary dilatation. CP-96,345 (10 microM) decreased the spontaneous sinus rate, prolonged the atrioventricular-nodal conduction interval and the His-bundle conduction interval of the perfused guinea-pig heart. The intraventricular spread of conduction was markedly inhibited. During programmed stimulation 10 min after the beginning of the drug application, the effective refractory periods evaluated by stimulation with premature beats, as well as rate dependent effective refractory periods, of the atrioventricular node, of the atrial and of the ventricular myocardium, were prolonged. Sinus node recovery time was also prolonged. It was concluded that these cardiac effects of CP-96,345 were not caused by an action of the compound on substance P receptors.
- Find related publications in this database (using NLM MeSH Indexing)
- Anesthesia -
- Animals -
- Biphenyl Compounds - pharmacology
- Blood Pressure - drug effects
- Decerebrate State - physiopathology
- Electrocardiography - physiopathology
- Electrophysiology - physiopathology
- Guinea Pigs - physiopathology
- Heart - drug effects
- Heart Rate - drug effects
- Hemodynamic Processes - drug effects
- Rats - drug effects
- Rats, Sprague-Dawley - drug effects
- Receptors, Neurokinin-1 - drug effects
- Receptors, Neurotransmitter - drug effects
- Substance P - antagonists and inhibitors