Sildenafil citrate is an inhibitor of the enzyme phosphodiesterase 5, dextromethorphan is an antitussive with weak opioid effects, and chlorpheniramine is a first-generation antihistamine. Since cardiovascular complications related to all three drugs have been reported, the aim of this study was to evaluate the serum levels of cardiac damage index enzymes and tropovinin I following co-administration of sildenafil with dextromethorphan and chlorpheniramine. Forty male Wistar rats were studied in 8 groups, one control group and the rest in the treatment group; Drugs sildenafil citrate (100 mg / kg), dextromethorphan (20 mg / kg), chlorpheniramine (20 mg / kg), dextromethorphan + chlorpheniramine, sildenafil + dextromethorphan, sildenafil + chlorpheniramine, sildenafil + rosemethor + dextrometer, Received food. The results showed that administration of sildenafil to rats did not cause statistically significant changes in serum cardiac injury indices compared with the control group (p < 0. 05); The amount of CK-MB also decreased compared to the control group. On the other hand, following administration of chlorpheniramine and dextromethorphan to rats, either alone or in combination, serum levels of AST, LDH and CK-MB increased statistically significantly. Administration of chlorpheniramine caused a significant increase in LDH (p < 0. 01) and CK-MB (p < 0. 001) compared to the control group and administration of dextromethorphan increased the activity of the studied enzymes which increased AST (p < 0. 05). ) And CK-MB (p < 0. 001) were significant. Co-administration of sildenafil with dextromethorphan and sildenafil with chlorpheniramine or all three together increased the activity of all three enzymes in the heart damage index.