Abstract: The protective effects of cyproheptadine, an antiserotonin-antihistaminic agentwith calcium channel blocker activity,on calcium paradox ih isolated Langendorff's heart in rats werestudied. After a 5 rain of calcium-free perfusion standard Krebs-Henseleit (K-H) buffer withoutcalcium, gassed with 95% O₂ and 5% CO₂ followed by a 20 min of normal K-H buffer (Ca²⁺ 2. 5mmol/L) perfusion, extensive and rapid myocardial injury was observed: release of massive cellularenzymes such as lactic dehydrogenase (LDH) and creatine phosphokinase (CPK). significant decreaseof myocardial anti-oxygen free radical enzymes such as superoxide dismutase (SOD) and glutathione. peroxidase (GSH-Px) activities but no obvious change of myocardial lipid peroxides such as malondial-dehyde (MDA) content was observed. The loss of normal colour and mechanical activity, even contrac-ture, was also observed in the injured hearts. Cyproheptadine(2. 5～5 μmol/L) was shown to effec-tively antagonize the damage. The results suggest that the protective effects of cyproheptadine on thecalcium paradox may be related to its actions of blockading calcium channel, protecting antioxygenfree radical enzymes and scavenging oxygen free radicals in the myocardial tissues.