BIOCHEMICAL-PROPERTIES OF BLOOD ESMOLOL ESTERASE

Abstract

[Esmolol is a novel, cardioselective ultra-short acting .beta.-blocker currently used in clinical trials]. The blood esterase mediating the hydrolysis of esmolol was characterized in several different species including man. In contrast to most ester-containing drugs, hydrolysis of esmolol was mediated by an esterase in the cytosol of red blood cells (RBC) in man and dogs and not in plasma or RBC membrane. Species differences in the esterase activity existed. Guinea pig and rat blood esterase activities were much greater than those in the dog followed by those in man. The esterase activity in rat and guinea pig blood was localized in plasma and not in RBC. Purified human serum cholinesterase, human RBC membrane acetylcholinesterase, human Hb, human carbonic anhydrases A and B and human and dog serum albumin were all inactive against esmolol. Esmolol esterase activity in human and dog blood was inhibited by NaF, EDTA and p-hydroxymercuribenzoate, but not by echothiophate, eserine and acetazolamide. Echothiophate and NaF , but not eserine, inhibited the esterase activity in rat and guinea pig plasma. Metabolic interaction studies indicated that acetylcholine, succinylcholine, procaine and chlorprocaine did not interfere with the metabolism of esmolol by human and dog blood. Apparently an arylesterase in human and dog RBC cytosol mediated the hydrolysis of esmolol while an aliphatic esterase mediated the hydrolysis of esmolol in guinea pig and rat plasma.