From the Department of Pharmacology, School of Medicine, Tehran Ulliversity of Medical Sciences, Tehran, l.R. Iran.
Abstract: (4456 Views)
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.