Disease relevance of torborinone

• Acute cardiovascular effects of OPC-18790 in patients with congestive heart failure. Time- and dose-dependence analysis based on pressure-volume relations [1].
• When these drugs produced the haemodynamic changes described above, amrinone and dobutamine reduced ATP and PCr, increased Pi and produced further intracellular acidosis, whereas, OPC-18790 did not change these parameters [2].
• Effects of OPC-18790, a new positive inotropic agent, on canine ventricular arrhythmias [3].
• We also examined the effects of OPC-18790 on ventricular arrhythmias in canine ventricular tachycardia (VT) models [3].
• Arrhythmias such as premature ventricular contraction developed in 5 out of 7 dogs (71.4%) in the 10-micrograms/kg/min dopamine group, while only one premature ventricular contraction was observed in 1 of 7 dogs (14.3%) in the OPC-18790 (10 micrograms/kg/min) and dopamine (5 micrograms/kg/min) combination group [4].

High impact information on torborinone

• Acute effects of toborinone on vascular capacitance and conductance in experimental heart failure [5].
• Data were collected at baseline, after induction of heart failure (microsphere embolization into the left coronary artery), and then after toborinone boluses of 0.1, 0.2, 0.4, and 0.8 mg/kg [5].
• CONCLUSIONS: OPC-18790 has potent venous and arterial vasodilator effects and moderate inotropic and lusitropic effects without a change in heart rate [1].
• We studied the contribution and relative dose sensitivities of the inotropic, lusitropic, and vascular effects of OPC-18790 in patients with dilated cardiomyopathy [1].
• CONCLUSION: These observed differences in energy metabolism between OPC-18790 and amrinone at the high dose may be due to the ability of OPC-18790 to increase CBF in the ischaemic region and which may attributed to its differing effect on overall haemodynamics [6].

Biological context of torborinone

• In vitro studies have shown that, in addition to its positive inotropic actions, OPC-18790 prolongs cardiac action potentials [7].
• Pharmacokinetics and pharmacodynamics of intravenous OPC-18790 in humans: a novel nonglycosidic inotropic agent [8].
• OPC-18790 significantly increased arterial blood flow distribution to heart and decreased vascular resistance in heart [9].
• A novel inotropic vasodilator, OPC-18790, reduces myocardial oxygen consumption and improves mechanical efficiency with congestive heart failure [10].
• Intravenously (i.v.) infused OPC-18790 increased the first derivative of left ventricular pressure (LVdP/dt max), cardiac output, heart rate and decreased total peripheral resistance but did not affect mean blood pressure [9].

Anatomical context of torborinone

• In rats, toborinone underwent O-demethylation to form M-7 and successive phase it reaction to yield the glucuronide M-1 and the sulfoconjugate M-2, and deconjugation to yield M-7, which was a primary metabolite accounted for 35.67% of the radioactivity excreted in the feces by 48 hr [11].
• These results suggest that toborinone modulates the action potential like an IK blocker rather than a PDE III inhibitor in a sinoatrial node [12].
• Toborinone produced concentration-dependent relaxation in preparations with, and those without functional endothelium [13].
• Calcium influx through calcium channels in the plasma membrane was also suppressed by toborinone and olprinone [14].
• OPC-18790 (10(-5) to 10(-4) M) prolonged the duration of action potential in guinea pig papillary muscles [15].

Associations of torborinone with other chemical compounds

• Amrinone and dobutamine but not OPC-18790 increased heart rate [2].
• In dogs, toborinone was metabolized via mercapturic acid pathway to yield the primary metabolites, cysteine conjugates M-10 and M-11 that accounted for 19.10% and 6.70% of the radioactivity excreted in the feces by 48 hr and that were detected species specifically in dogs [11].
• Biotransformation of the novel inotropic agent toborinone (OPC-18790) in rats and dogs. Evidence for the formation of novel glutathione and two cysteine conjugates [11].
• This study investigated the effects of the concomitant administration of theophylline and toborinone on the pharmacokinetics of both compounds in poor and extensive metabolizers via CYP2D6 [16].
• Milrinone increased heart rate (HR) by 22 +/- 4% but toborinone did not change HR [17].

Gene context of torborinone

• No significant differences were observed in toborinone pharmacokinetics between poor and extensive metabolizers via CYP2D6 [16].
• The ratio of external work to the pressure-volume area (EW/PVA) was similarly increased by both drugs, resulting in an improvement in mechanical efficiency (EW/MVo2) with OPC-18790 (p < 0.05) and in a deterioration with dobutamine (p < 0.05) [10].
• Toborinone ((+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-qui nolinone, CAS 128667-95-8, OPC-18790), a novel cardiotonic agent with an inhibitory action on phosphodiesterase, is known to have a potent positive inotropic action with no positive chronotropic effect [18].

Analytical, diagnostic and therapeutic context of torborinone

• These combined actions suggest a unique potential of OPC-18790 for heart failure treatment [1].
• OPC-18790 in doses producing submaximal inotropic effects, 3 mg/kg, i.v., increased the total heart rate, atrial rate and decreased the blood pressure, but did not suppress or aggravate 24- and 48-hr coronary ligation VTs [3].

References