Mechanism of inhibitory effect of citalopram on isolated guinea‐pig atria in relation to adenosine receptor

Abstract

The effect of citalopram (CTP), a selective serotonin reuptake inhibitor antidepressant was studied on the rate and force of contractions of isolated guinea-pig atria. CTP (2-32 microg/ml) caused a dose-dependent decrease in the contractile force (7%-62%) and in the rate of contractions (11%-72%). These negative inotropic and chronotropic effects of CTP (8 microg/ml) were not prevented by atropine (1 microg/ml) and 3,7 dimethyl-1-propargylxanthine (DMPX; 1.5 microg/ml), an adenosine A(2) receptor antagonist, but 1,3 dipropargyl-8-cyclopentylxanthine (DPCPX; 12 microg/ml), a specific adenosine A(1) receptor antagonist significantly blocked these effects (p < 0.001) and theophylline (30 microg/ml) a non-selective adenosine A(1)/A(2A) receptor antagonist also prevented the inotropic and chronotropic effects of CTP. These results suggest that the negative inotropic and chronotropic effect of CTP on isolated guinea-pig atria is probably mediated through an inhibition of the uptake of adenosine or the A(1) receptor mechanism.

Blinded Contractility Analysis in hiPSC-Cardiomyocytes in Engineered Heart Tissue Format: Comparison With Human Atrial Trabeculae

“…The negative inotropic effect of citalopram is likely independent of the primary mechanism of action (SSRI) and in line with a published report in isolated guinea-pig atria suggesting that citalopram mediates A1 adenosine receptor agonistic effect ( Pousti et al , 2004 ). The potency (IC 50 : 10 µM) suggests that this effect is not relevant under normal antidepressant treatment (plasma concentration 300 nM; Gutierrez and Abramowitz, 2000 ).…”

Immunotropic effects of so-called slag metabolites (creatinine, urea, uric acid and bilirubin) at rats

“…It is known that the immunotropic effect of adenosine is realized through its receptors (A1, A2A, A2B, A3), which express virtually all populations of immunocytes: T, NK, B lymphocytes, macrophages, neutrophils, dendritic and endothelial cells [1,22,23,42]. Methylxanthines are nonselective antagonists of adenosine receptors, mainly A2A and A1 [8,28,29,30,35]. The facts obtained in our [19,20] previous human studies on the inversely relationship of uricemia (the level of which is comparable to the concentrations of adenosine and theophylline in immune tests in vitro) with a relative blood content of CD4 + CD3 + T-helper cells in combination with the presence of directly connection with the content of CD8 + CD3 + T-cytolytic cells indicate the similarity of the effects of uric acid with those of adenosine, ie activation of A2A receptors.…”

Relationships between changes in uric acid parameters metabolism and parameters of immunity and microbiota in patients with neuroendocrine-immune complex dysfunction

“…Theophylline (2,6-dioxi-1,3-dimethylpurine or 1,3-dimethylxantine) is a structural homolog of Adenosine [(2R,3R,4R,5R)-2-(6-aminopurine-il)-5-(hydroximethyl) oxolan-3,4-diol)] and capable of 0,2 mM/L at blocking adenosine А1-і А2А receptors [25].…”