Medical Journal of The Islamic Republic of Iran (MJIRI)

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Carbamazepine, a drug effective in pain, seizure, and affective disorders, was studied for its effects and toxicity on spontaneously beating isolated guinea pig atria, Carbamazepine (20-􀁽0 J.lg/mL) has a negative chronotropic effect on artria, without any significant effect on contractile force. The most significant effect (12.5%) was seen with 30 J.lg/mL of carbamazepine on atria. With higher doses (>30 µg/mL) carbamazepine produced toxic effects which resulted in atrial standstill. Pretreament of atria with theophylline (5-5 0 µg/mL) prevented the negative chronotropic effect of carbamazepine (30 µg/mL). Three dose ratios of carbamazepine (1.33,2,2.33) in the presence of three different doses of theophylline (30,50 and 60 µg/mL) were obtained. These results suggest that the negative chronotropic effect of carbamazepine and its toxicity may be due to its action as an agonist on adenosine Al receptoCarbamazepine, a drug effective in pain, seizure, and affective disorders, was studied for its effects and toxicity on spontaneously beating isolated guinea pig atria, Carbamazepine (20-􀁽0 J.lg/mL) has a negative chronotropic effect on artria, without any significant effect on contractile force. The most significant effect (12.5%) was seen with 30 J.lg/mL of carbamazepine on atria. With higher doses (>30 µg/mL) carbamazepine produced toxic effects which resulted in atrial standstill. Pretreament of atria with theophylline (5-5 0 µg/mL) prevented the negative chronotropic effect of carbamazepine (30 µg/mL). Three dose ratios of carbamazepine (1.33,2,2.33) in the presence of three different doses of theophylline (30,50 and 60 µg/mL) were obtained. These results suggest that the negative chronotropic effect of carbamazepine and its toxicity may be due to its action as an agonist on adenosine Al receptors and as an antagonist on A2 receptors of the atria. Moreover, using adenosine antagonists such as theophylline may overcome the toxic effect of carbamazepine on the heart. This may explain the reason for the interaction between carbamazepine and theophylline in clinical settings.

Keywords: Carbamazepine, isolated atria. theophylline, adenosine receptors.

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