human psychopharmacology Hum Psychopharmacol Clin Exp 2004; 19: 347–350. Published online 27 May 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hup.593 Mechanism of inhibitory effect of citalopram on isolated guinea-pig atria in relation to adenosine receptor Abbas Pousti 1 *, Tara Deemyad 1 and Golrokh Malihi 2 1 Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran 2 Department of Pharmacology, Shahid Beheshti University of Medical Sciences, Tehran, Iran 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 mg/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 mg/ml) were not prevented by atropine (1 mg/ml) and 3,7 dimethyl-1-propargylxanthine (DMPX; 1.5 mg/ml), an adenosine A 2 receptor antagonist, but 1,3 dipropargyl-8-cyclopentylxanthine (DPCPX; 12 mg/ml), a specific adenosine A 1 receptor antagonist sig- nificantly blocked these effects ( p < 0.001) and theophylline (30 mg/ml) a non-selective adenosine A 1 /A 2A receptor antago- nist 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. Copyright # 2004 John Wiley & Sons, Ltd. key words — citalopram; guinea-pig isolated atria; adenosine receptor INTRODUCTION There are four recognized subtypes of adenosine receptors: A 1 ,A 2A ,A 2B and A 3 (Fredholm et al., 2001; Auchampach and Bolli, 1999; Olah and Stiles; 1995). The experiments in guinea-pig cardiac pre- parations present evidence that A 1 adenosine recep- tors agonists cause a negative chronotropic effect by slowing the pacemaker rate in the sinus nodes (West et al., 1987) and in the left atria a direct negative ino- tropic effect due to an activation of a potassium out- ward current (Wang and Belardinellli, 1994). These effects were abolished by the A 1 adenosine receptor antagonist DPCPX (Vahlensieck et al., 1999). The A 1 adenosine receptors appear to act on many effec- tors as a ‘second messenger system’. These receptors mediate the inhibition of G proteins and adenylyl cyclase (Shryock and Belardinelli, 1997) activation of several types of K þ channels and inactivation of N-P and Q type Ca 2þ channels. Adenosine is indicated for the prompt conversion of the paroxysmal supra- ventricular tachycardia to sinus rhythm, slowing the ventricular rate during atrial fibrillation and as an adjunct to thallium cardiac imaging in the evaluation of coronary artery disease in patients unable to exer- cise adequately (Fredholm et al., 2001). There are reports that adenosine receptors are widely distributed both in the brain and peripheral tissues (Dixon et al., 1996). The antinociceptive activity of several antide- pressants was antagonized by the non-selective blocker of A 1 /A 2A adenosine receptor aminophylline (Sierralta et al., 1995). Previously it was shown that CTP (citalopram) caused a negative inotropic and chronotropic effect on isolated guinea-pig atria (Pousti et al., 2003b); these effects of CTP are like adenosine A 1 receptor agonists on isolated atria. The present study was therefore designed to clarify whether adenosine receptors may be involved in med- iating the effects of CTP on isolated guinea-pig atria. MATERIALS AND METHODS Guinea-pigs of either sex weighing 400–600 g were anaesthetized with ether and killed by exsanguination. The heart was rapidly removed, the atrium was dis- sected out in oxygenated modified Krebs solution Received 23 January 2004 Copyright # 2004 John Wiley & Sons, Ltd. Accepted 15 March 2004 * Correspondence to: Dr A. Pousti, Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran. Tel: þ9821 223 6334. Fax: þ9821 640 2569. E-mail: drpousti@yahoo.com Contract/grant sponsor: Medical School of Tehran University of Medical Sciences.