Abstract

The cardiovascular effects of D-Ala-2-Me-Phe-4-Met-(O)-01 enkephalin were investigated after its administration into the fourth cerebroventricle of the guinea pig. This enkephalin is a synthetic Met-enkephalin analog that is more resistant to degradation and has a high affinity for opioid receptors. It produced a significant increase in blood pressure and decline in heart rate. At high concentrations, 100 ug/kg plus 100 ug/kg/hr in the fourth ventricle, it produced bradyarrhythmias that were sometimes fatal. At doses that did not alter survival or produce arrhythmia, namely 30 ug/kg plus 25 ug/kg/hr in the fourth ventricle, the response to digitalis was assessed. Significant leftward shifts in the relationships between digoxin and arrhythmia occurrence and development of fatal arrhythmias were observed. Thus, D-ala-2-Me-Phe-4-Met-(O)-01 enkephalin has definite cardiovascular effects that include potentiation of digoxin arrhythmias.

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