Disease relevance of AQ-A 39

• The results suggest that AQ-A 39 will be useful in the short term management of patients with ischaemic heart disease [1].
• Thus falipamil can be used to normalize sinus rate in patients with sinus tachycardia of various origin, particularly in intensive care, in acute ischaemic heart disease, in anaesthesia and in surgery cases [2].
• The rise of heart rate induced by orthostasis was diminished by AQ-A 39 to 4 +/- 2 beats min-1 and by propranolol 9 +/- 2 beats min-1 [1].
• AQ-A 39 prevented the tachycardia by both slowing of AV nodal conduction and by prolongation of action potential duration in the AV nodal and atrial compartments of the reentrant circuit associated with the appearance of different gap phenomena of the AV conduction [3].
• In isolated guinea-pig atria UL-FS 49 antagonized the carbachol-induced bradycardia; a 10-fold shift of the dose-response curve (CA10) was achieved with 11.3 micrograms/ml and the CA10 for AQ-A 39 was 1.7 micrograms/ml [4].

High impact information on AQ-A 39

• In a randomized, controlled study 10 male patients with angiographically confirmed ischaemic heart disease received AQ-A 39 (falipamil), a heart rate reducing agent in a single intravenous dose (2 mg kg-1) in comparison to propranolol (0.1 mg kg-1) [1].
• After submaximal exercise heart rate during placebo was 129 +/- 3, during AQ-A 39 113 +/- 3 and during propranolol 103 +/- beats min-1 [1].
• Falipamil causes a slight prolongation of intraatrial and intraventricular conduction, whereas sinuatrial and AV-node conduction is enhanced [2].
• The dose of isoproterenol necessary to induce an increase of heart rate by 20 beats min-1 was after AQ-A 39 4.2 times greater and following propranolol 9.2 times greater than during placebo [1].
• Effect of nifedipine and AQ-A 39 on the sinoatrial and atrioventricular nodes of the rabbit and their antiarrhythmic action on atrioventricular nodal reentrant tachycardia [3].

Chemical compound and disease context of AQ-A 39

• Comparison of AQ-A 39 with propanolol and placebo in ischaemic heart disease [1].
• 1. v. administration of 5,6-dimethoxy-2-(3-[(alpha-(3,4-dimethoxy) phenylethyl) methylamino] propyl)- phthalimidine (AQ-A 39) to anaesthetized animals induced dose dependents bradycardia [5].

Biological context of AQ-A 39

• 100 mg falipamil was followed by a 9% reduction in heart rate [6].
• Neither falipamil nor alinidine modified mean blood pressure in either group [7].
• Pharmacokinetics of falipamil after intravenous administration to humans [8].
• On systemic administration, total peripheral resistance was significantly increased with alinidine, significantly decreased with AQ-A 39, and not affected with mixidine [9].
• Increases in stroke volume accompanied bradycardic responses to AQ-A 39 and mixidine, and were prevented when heart rate was held constant by electrical pacing [9].

Anatomical context of AQ-A 39

• In paced papillary muscle preparations, AQ-A 39 reduced force of contraction only in large doses (1-3 mg) [10].
• These results show that the bradycardic effects of AQ-A 39 and alinidine are diminished in depolarized preparations, which makes it unlikely that in intact sinus node preparations the mechanism of action is the same as that of "Ca2+-antagonists" [11].
• In cats with acute occlusion of a coronary artery branch, AQ-A 39 diminished the elevation of the ST-segment of the epicardial electrogram [12].
• Chronotropic cardiac effects of falipamil in conscious dogs: interactions with the autonomic nervous system and various ionic conductances [13].
• In the Ba2+ treated depolarized myocardium Vmax was considerably reduced by AQ-A 39 [14].

Associations of AQ-A 39 with other chemical compounds

• The results suggest that nifedipine and AQ-A 39 both have a direct depressant action on the slow inward current-dependent electrical activity of the SA and AV node but have opposite effects on the repolarisation phase resulting in different antiarrhythmic mechanisms [3].
• In the ECG of anaesthetized cats (0.1-10 mg/kg i.v.) the prominent effect of AQ-A 39 was the increase in heart period (PP') and QT in contrast to the chemically related verapamil which mainly increased PQ [12].
• Each dog received, with at least a three-day interval, falipamil (hydrochloride) and alinidine (hydrobromide) in four successive intravenous injections, 30 min apart, at 0.5, 0.5, 1, and 2 mg kg-1 [7].
• 5,6-Dimethoxy-2-((3[(alpha-(3,4-dimethoxy) phenylethyl)-methylamino]propyl))-phthalimidine hydrochloride (AQ-A 39 Cl, in the following briefly called AQ-A 39) is a new compound with a structure similar to that of verapamil and which exhibits a specific bradycardic effect by a direct action on the sinus node [15].
• The observed order of depression of inotropism was verapamil greater than diltiazem greater than bepridil = dilazep greater than AQ-A 39, while the order of negative chronotropism was diltiazem greater than verapamil greater than AQ-A 39 greater than dilazep greater than bepridil [16].

Gene context of AQ-A 39

• The parent drug, falipamil (1), and its N-desmethyl-metabolite (2), which is approximately 100 times less active than 1, contributed 14.1 +/- 1.6 and 4.5 +/- 0.7%, respectively, of the dose to urinary excretion [8].

Analytical, diagnostic and therapeutic context of AQ-A 39

• Beneficial effects of two specific bradycardic agents AQ-A39 (falipamil) and AQ-AH 208 on reversible myocardial reperfusion damage in anesthetized dogs [17].
• Pharmacokinetics of falipamil in humans (n = 6) was determined in plasma and urine after iv administration of 100 mg (1.85 MBq) per person of 14C-labeled drug by liquid scintillation counting and by a specific, sensitive reversed-phase totally automated HPLC system with fluorimetric detection [8].

References