These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The inotropic and beta blocking effects of a chimeric molecule that putatively inhibits both type III phosphodiesterase and beta adrenoceptors in anesthetized dogs.
    Author: Shaffer JE, Grizzle MK, Anderson DK, Wheeler TN.
    Journal: J Pharmacol Exp Ther; 1993 Jun; 265(3):1105-12. PubMed ID: 8099617.
    Abstract:
    The hemodynamic and beta adrenergic blocking effects of GI104313, a chimeric molecule containing a phosphodiesterase-inhibiting pyradazinone and a beta blocking phenoxpropanolamine, were examined in barbiturate-anesthetized, vagotomized dogs. The results of these studies were compared to those of indolidan, a known phosphodiesterase inhibitor, and xamoterol, a partial beta adrenoceptor agonist. The compounds were infused at six increasing dose rates in 10-min intervals. Isoproterenol (0.5 microgram/kg) was administered before each dose increment to determine beta adrenoceptor responsiveness. In a separate set of experiments, the hemodynamic effects of GI104313, indolidan and xamoterol were examined in the presence of complete beta blockade with atenolol. GI104313 elicited dose-dependent increases in heart rate, contractility (+dP/dt) and cardiac output and decreases in arterial blood pressure, left ventricular end diastolic pressure and systemic vascular resistance in unpretreated and atenolol-pretreated dogs. However, GI104313 was less potent hemodynamically in atenolol-pretreated animals. This was evidenced by a 4-fold dextral shift in the dose-response relation for several hemodynamic variables. In unpretreated dogs, GI104313 elicited potent dose-dependent blockade of the heart rate, diastolic blood pressure and +dP/dt responses to isoproterenol. Greater than 95% inhibition of isoproterenol response was attained at 1 mumol/kg GI104313 for all observed variables. Indolidan increased contractility and heart rate and decreased diastolic blood pressure in a dose-related fashion. Indolidan did not modify the stimulatory effects of isoproterenol. Atenolol had modest effects on indolidan's hemodynamic effect, only shifting its inotropic effect 2-fold. Xamoterol produced hemodynamic and beta blocking effects similar to GI104313.(ABSTRACT TRUNCATED AT 250 WORDS)
    [Abstract] [Full Text] [Related] [New Search]