Detail of "34368-04-2"

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Cardiovascular effects of KM-13, a new, orally effective, cardiotonic sympathomimetic amine

Cardiovascular effects of KM-13, a new, orally effective, cardiotonic sympathomimetic amine. Caldwell, Robert W.; Nash, Clinton B.; Smulkowski, Maciej; Tuttle, Ronald R. (Dep. 108278-57-5 and 99450-08-5 are also occured in this study. Pharmacol., Univ. Tennessee, Memphis, TN 38163, USA). J. Cardiovasc. Pharmacol., 9(3), 375-84 (English) 1987. CODEN: JCPCDT. ISSN: 0160-2446. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The structure of dobutamine [34368-04-2] was modified to make it orally effective, while its pharmacol. profile was preserved. Testing on anesthetized dogs showed that replacement of the para hydroxyl group with carboxyamide at the Ph end of the mol. increased inotropic potency 3-fold, but it introduced pressor activity that spoiled the inotropic selective profile of dobutamine. However, shifting carboxyamide to the meta position avoided pressor activity and further enhanced inotropic potency to 9-times that of dobutamine. When administered orally to conscious dogs, this compd., KM-13 (I) [97816-65-4] (5 mg/kg), produced a sustained increase in left ventricular dP/dt with only immediate changes in heart rate; 10 mg/kg dobutamine was without cardiovascular effects. The (-) isomer of KM-13 [108278-58-6] contained twice the inotropic activity of the (+) isomer [108278-57-5]; in contrast, the (-) isomer had no effect on diastolic blood pressure, while the (+) isomer lowered blood pressure. The inotropic and chronotropic effects of dobutamine and KM-13 are both largely due to b-adrenergic stimulation as shown by propranolol blockade. In contrast to dobutamine, KM-13 is an agent that is active by either oral or buccal administration and has greater inotropic potency. .

Additive and non-additive positive inotropic effects in human and guinea pig myocardium

Additive and non-additive positive inotropic effects in human and guinea pig myocardium. Brown, Lindsay; Lorenz, B.; Erdmann, E. (Med. Klin. I, Ludwig-Maximilians-Univ. Muenchen, Munich 8000/70, Fed. Rep. Ger.). Card. 630-60-4 and 7683-59-2 are cas registry numbers. These chemicals are also mentioned in this article. Glycosides 1785--1985, 195-205. Edited by: Erdmann, Erland; Greeff, Kurt; Skou, Jens C. Steinkopff: Darmstadt, Fed. Rep. Ger. (English) 1986. CODEN: 55MWAM. DOCUMENT TYPE: Conference CA Section: 1 (Pharmacology) Section cross-reference(s): 2 The pos. inotropic effects of b-agonists (isoprenaline [7683-59-2], dobutamine [34368-04-2], dopamine [51-61-6]), histamine [51-45-6], phosphodiesterase inhibitors (isobutylmethylxanthine [28822-58-4], milrinone [78415-72-2], theophylline [58-55-9]), ouabain [630-60-4], and Ca2+ were measured using contracting papillary muscles from healthy guinea-pig hearts as well as on contracting papillary muscle strips from patients undergoing mitral valve replacement. In the guinea-pig myocardium, the potencies varied markedly, but all compds. gave the same maximal increase in force of contraction. In contrast, compds. acting through cAMP gave maximal pos. inotropic effects which were significantly reduced compared with ouabain and Ca2+ in human papillary muscle strips. Further, the potency of b-agonists was decreased in the diseased human ventricular myocardium. Either b-agonists, histamine, or phosphodiesterase inhibitors were added after a stable, almost maximally effective but non-toxic effect of ouabain had been achieved. The maximal inotropic response to combined treatment was not greater than to either compd. alone in the guinea-pig heart; the only increase was in the incidence of toxicity. In human papillary muscle strips, the maximal effect of ouabain could not be increased by any other compd., but the reduced maximal effect of dobutamine could be increased by the addn. of ouabain. These results indicate that addnl. inotropic effects are not solely responsible for the hemodynamic improvements after combined inotropic therapy in optimally digitalis-treated patients. Other cardiovascular effects such as cAMP-induced vasodilatation must also be considered. .