Drugs online research references
Eur J Pharmacol. 1994 Mar 11;254(1-2):141-50.
Thaliporphine, a positive inotropic agent with a negative chronotropic action.
Su MJ, Chang YM, Chi JF, Lee SS.
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
The effects of thaliporphine on contractions and electrophysiological properties of cardiac tissues were examined. In driven rat left atria and right ventricular strips, thaliporphine (1-30 microM) increased twitch tension dose-dependently. The positive inotropic effect of thaliporphine was unaffected by atenolol (3 microM) and prazosin (1 microM) but was significantly suppressed by verapamil (1 microM). An electrophysiological study revealed that thaliporphine (3-10 microM) markedly inhibited the action potential upstroke and prolonged the action potential duration (APD50) in rat and guinea pig atrial and ventricular cells. At 1-30 microM, thaliporphine reduced the transient outward current (Ito) of the rat ventricular cells in a dose-dependent manner. The peak Ito in rat ventricular cells and the delayed rectifying K+ current (Ik in guinea pig ventricular cells were reduced by thaliporphine (10 microM) to 37.3 +/- 2.1% (n = 8) and 45.3 +/- 1.8% (n = 4), respectively. In rat ventricular cells and guinea pig atrial cells, thaliporphine (1.5 microM) reduced the Na+ inward current (INa) with a negative shift (4-5 mV) relative to its half inactivation potential. For the Ca2+ inward current (ICa) in rat ventricular cells, 10 microM of thaliporphine caused a smaller increase in the peak ICa than 0.5 microM of Bay K 8644. The increase in ICa elicited by both agents was associated with a negative shift of its half activation potential from -10 +/- 2 mV to -18 +/- 2 mV (n = 6) by thaliporphine and -11 +/- 2 to -19 +/- 2 mV (n = 4) by Bay K 8644. These results indicate that thaliporphine is a weak Ca2+ channel agonist with strong Na+ and K+ channel blocking activities. The positive inotropic effect may be due to an increase in calcium entry mediated via partial activation of calcium channels or by inhibition of K+ efflux. Inhibition of K+ efflux would result in prolongation of APD50 and contribute to the negative chronotropic effect of thaliporphine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7515818&dopt=Abstract
J Cardiovasc Pharmacol. 1989 Oct;14(4):519-25.
Comparative positive inotropic effects of TA-064 (denopamine), a new cardiotonic agent, and isoproterenol and ouabain on guinea pig ventricular muscles.
Sato T, Imanishi S, Arita M.
Department of Physiology, Medical College of Oita, Japan.
The effects of TA-064 (TA) on "fast" and "slow" response action potentials and contractile tensions were studied in isolated guinea pig papillary muscles, and the findings were compared with those of isoproterenol (ISP) and ouabain. The results are as follows: (a) TA produced a dose-dependent (10(-7)-10(-5) M) increase in developed tension, with no significant changes in the resting membrane potential (RMP), action potential duration (APD), and maximum rate of rise of action potential (Vmax). (b) The concentration required to increase the developed tension by threefold ("equivalent concentration") were 10(-6) M with both TA and ouabain, while that of ISP was 5 x 10(-8) M. (c) TA increased the maximum rate of rise, dP/dtmax, and the maximum rate of fall, dR/dtmax, of the developed tension to the same extent, unlike those of ISP and ouabain. (d) Positive inotropic effects of TA (10(-7)-10(-5) M) were not completely abolished by atenolol (3.8 x 10(-5) M), a specific beta 1 blocker, whereas those of ISP were completely abolished. (e) The increasing effects of "equivalent concentration" of TA (10(-6) M) on the Vmax of the slow response were less than those of ISP (5 x 10(-8) M). These results suggest that the positive inotropic effects of TA are mainly due to stimulation of beta 1 adrenoceptors, but that the mode of action of the drug differs in several respects from that of ISP or ouabain.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2478764&dopt=Abstract
Naunyn Schmiedebergs Arch Pharmacol. 1992 Jul;346(1):82-7.
Electrophysiologic and inotropic effects of alpha-adrenoceptor stimulation in human isolated atrial heart muscle.
Jahnel U, Jakob H, Nawrath H.
Pharmakologisches Institut, Universitat Mainz, Federal Republic of Germany.
The effects of alpha-adrenoceptor stimulation on force of contraction were investigated in human atrial heart muscle and compared with those of beta-adrenoceptor stimulation. The maximal positive inotropic effect produced by stimulation of alpha-adrenoceptors with phenylephrine (in the presence of atenolol 10 mumol/l) was significantly smaller than that seen in response to beta-adrenoceptor stimulation with isoprenaline. The maximal effect of phenylephrine (25% of the maximal effect of isoprenaline) required far higher concentrations (1 mmol/l) than isoprenaline (100 nmol/l); the EC50 values amounted to 33.1 mumol/l and 3.3 nmol/l, respectively. In the presence of the alpha-adrenoceptor blocking agent phentolamine (1 mumol/l), the concentration-response curve of phenylephrine was displaced to higher concentrations of the agonist; under these conditions, the EC50 value amounted to 52.5 mumol/l. The effects of the catecholamines noradrenaline and adrenaline on force of contraction remained unchanged in the presence of phentolamine (1 mumol/l) or prazosin (1 mumol/l). The positive inotropic effect of phenylephrine (1 mmol/l) was associated with a slight decrease in action potential duration; the effects on action potential were completely blocked in the presence of phentolamine (1 mumol/l). These findings support the view that selective stimulation of alpha-adrenoceptors may mediate a small but detectable positive inotropic effect in human atrial tissue under in vitro conditions. The requirement of high concentrations of alpha-adrenoceptor agonists and the lack of effects of the endogenous catecholamines adrenaline and noradrenaline on alpha-adrenoceptors (in concentrations which fully elicit the beta-adrenoceptors-mediated response) do not provide a basis for a functional role of alpha-adrenoceptor-mediated effects under in vivo conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1328895&dopt=Abstract
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