Cardiovascular effects of a newly synthesized cardiotonic agent (TA-064) on normal and diseased hearts

• Published in: The American journal of cardiology Vol. 51; no. 5; pp. 802 - 810
• Main Authors: Kino, Masaya, Hirota, Yuzo, Yamamoto, Shoji, Sawada, Kenichi, Moriguchi, Masatomo, Kotaka, Masahiro, Kubo, Shinichiro, Kawamura, Keishiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-1983
• Subjects: Adult; Aged; Blood Pressure; Cardiac Output; Cardiotonic Agents - therapeutic use; Echocardiography; Ethanolamines - therapeutic use; Heart Failure - diagnosis; Heart Failure - drug therapy; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Stroke Volume
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/S0002-9149(83)80137-4

A new inotropic agent, TA-064, (−)-
α-(3,4-dimethoxyphenethylaminomethyl)-4-hydroxybenzylalcohol, was shown to have strong effects in experimental animals. Its effectiveness and associated adverse effects were tested in humans invasively (n = 6) and noninvasively (n = 17). Increasing doses of intravenous infusion (1, 2, and 4
μg/kg/min) increased plasma levels to 15, 35, and 82 ng/ml, respectively, resulting in marked increases in the peak rate of left ventricular pressure rise (dP/dt) (1,450 ± 63 to 3,042 ± 349 mm Hg/s) (mean ± standard error of the mean [SEM], p <0.01) and the ratio of dP/dt to left ventricular pressure at a developed pressure of 40 mm Hg (25 ± 3 to 39 ± 2 s
−1) (p <0.01), with a reduction in left ventricular end-diastolic pressure (12 ± 2 to 4 ± 1 mm Hg) (p <0.01). Minimal or no changes were seen in heart rate and left ventricular systolic pressure. After a single oral dose (10 mg), the plasma level reached its peak at 90 minutes (16 ± 9 ng/ml, n = 17). A positive inotropic effect was confirmed echocardiographically in both healthy volunteers (n = 8) and patients with congestive heart failure (CHF) (n = 9) who were maximally treated with conventional regimens: increase in mean velocity of circumferential fiber shortening (healthy volunteers: 1.29 ± 0.05 to 1.60 ± 0.11 circ/s [p < 0.05]; patients with CHF: 0.69 ± 0.08 to 0.93 ± 0.09 circ/s [p <0.01]), ejection fraction (healthy volunteers: 68 ± 2 to 75 ± 2% [p <0.05], patients with CHF: 37 ± 4 to 45 ± 5% [p <0.01]) without change in heart rate. The cardiac index was increased only in the CHF group (2.71 ± 0.22 to 3.21 ± 0.24 liters/min/m
2) (p <0.05). No significant untoward effects were observed. Thus TA-064 is a potent inotropic agent and can be used either parenterally or orally. Salutary effects can be expected in patients with congestive heart failure who are treated with digitalis and diuretic agents.