Effects of dimebon on coronary blood flow and myocardial contractility

Abstract

The antihistamine Dimebon, which is an Hi-receptor blocker, is shown to act as a moderate coronary vasodilator without exerting a marked effect on myocardial contractility. Key Words: Dimebon; coronary blood flow; myocardial contractilityA major problem in cardiology is sudden cardiac death, which is often preceded by ventricular arrhythmias due to inadequate coronary circulation [7]. Recently, we reported evidence that the Russianmade antihistamine Dimebon (Hi-receptor blocker) exhibits, in various animal models, an antiarrhythmic activity superior to that of quinidine, Ethmosine, Bonnecor, and verapamil [2]. Our present study is the first in which Dimebon was tested for its effects on coronary blood flow (CBF) and myocardial contractility. MATERIALS AND METHODSPhasic changes in CBF were examined in five dogs with open chest [4] after an intravenous injection of Dimebon at 2.5 mg/kg body weight. The following parameters were measured: heart rate, left ventricular and aortic pressures, perfusion pressure in coronary vessels at the end of diastole, stroke systolic CBF, stroke diastolic CBF, coronary index (ratio of the stroke diastolic CBF to the stroke systolic CBF), stroke CBF, minute CBF, and resistance of coronary vessels at the end of diastole. Myocardial contractility was evaluated from the level of intraventricular pressure and the rate of its change (AP/Atox) and also by measuring the acceleration developed by the myocardium [5]. Department of Pharmacology, Kuban Medical Academy, KrasnodarThe effect of intravenous Dimebon (2.5 mg/kg) on myocardial contractility was tested on seven artificially ventilated cats with [3-adrenoceptors blocked by Obsidan (1 mg/kg intravenously). In these cats we additionally determined the phasic structure of the cardiac cycle by measuring the lengths of the asynchronous contraction phase, isometric contraction phase, tension period, ejection period, total systole, and left ventricular diastole [3].The effect of Dimebon on the electrical and contractile properties of coronary vessels was examined in vitro using 12 isolated segments of porcine coronary arteries [6] exposed to a hyperpotassic solution or to serotonin.The data were statistically analyzed as described by Belen'kii [1]. RESULTSDimebon administration to dogs led to significant rises in the heart rate by 3.7%, stroke systolic CBF by 68.8%, stroke diastolic CBF by 42.2%, stroke CBF by 49.5%, and minute CBF by 52.6%, and to a 48.6% increase in the acceleration developed by the myocardium; the aortic and perfusion pressures significantly decreased by 6.9% and 12.3%, respectively (Fig. 1).Variations in the other two parameters (coronary index and AP/At ) in response to Dimebon were insignificant, which should be interpreted as an indication of its beneficial cardiotropic action. It is

Antihistamine Agent Dimebon As a Novel Neuroprotector and a Cognition Enhancer

“…Based on the results of these studies, Dimebon was classified as a low toxic substance. A pronounced antiarrhythmic effect of Dimebon and its beneficial effect in certain heart conditions have also been emphasized 21–23…”

“…A pronounced antiarrhythmic effect of Dimebon and its beneficial effect in certain heart conditions have also been emphasized. [21][22][23] In summary, Dimebon has a combination of pharmacological and safety properties that suggest the drug as a candidate for the use in the therapy of Alzheimer's disease. The results of the study reported here show that Dimebon has a great potential as a new medication that may not only improve cognitive functions, but, most importantly, may prevent the progression of the disease.…”

Latrepirdine: molecular mechanisms underlying potential therapeutic roles in Alzheimer’s and other neurodegenerative diseases

“…However, its use as an antihistamine declined with the discovery of more selective drugs. 6 , 23 Studies also have reported antiarrhythmic properties and an effect on coronary blood flow and myocardial contractibility, 24 , 25 even though the possible underlying mechanisms have not yet been determined. More recently, interest in latrepirdine rebounded following a growing interest in the role of histamine receptors (5-hydroxytryptamine 6 (5-HT6) and 5-HT7) in learning and cognitive functions 26 , 27 and studies reporting cognitive-enhancing and neuroprotective functions of latrepirdine.…”

Dimebon Inhibits Calcium-Induced Swelling of Rat Brain Mitochondria But Does Not Alter Calcium Retention or Cytochrome C Release

“…Dimebon (Latrepiridine; 2,3,4,5-tetrahydro-2,8-dimethyl-5-(2-(6-methyl-3-pyridyl)ethyl)-1 H -pyrido(4,3-b)indole)) was introduced as an antihistamine in Russia in 1983 (Mateeva 1983) and was subsequently investigated as a possible therapeutic for a variety of disorders (Shadurskii et al 1983; Galenko-Iaroshevskii et al 1995, 1996). Based on its neuroprotective and cognitive-enhancing properties in the CNS (Shadurskaia et al 1986; Lermontova et al 2000; Bachurin et al 2001; Lermontova et al 2001), Dimebon was investigated as a possible treatment for Alzheimer's disease (Doody et al 2008).…”