Related Experiment Video
Updated: Sep 10, 2026

Functional Characterization of Carboxylesterases in Insecticide Resistant House Flies, Musca Domestica
Published on: August 23, 2018
Species differences in the hydrolysis of meperidine and its inhibition by organophosphate compounds
1Department of Pharmacology, Eastern Virginia Medical School, Norfolk 23501.
Abstract:
The hydrolysis of meperidine was assayed in washed, unfortified liver microsomal fractions of guinea pig, rat, mouse, dog, and human, by following substrate disappearance as quantitated by high-performance liquid chromatography. Using the method of Lineweaver-Burk plots, the velocity of the meperidine hydrolysis reaction was not detectable in guinea pig, very low in human, and extremely high in dog. Hydrolysis of p-nitrophenyl acetate was also monitored in liver microsomal preparations from the same animal species, with guinea pig showing greatest hydrolytic activity and rat showing least hydrolytic activity for this substrate. The data in the above two assays suggested that meperidine hydrolysis is mediated by a unique esterase not present in guinea pig and very low in human, but present with high activity in dog liver microsomes. From these comparative studies we concluded that liver microsomes from different species may contain different carboxylesterases having different affinities for meperidine. To further characterize meperidine carboxylesterase of dog and rat liver microsomes, inhibitory studies in vitro with two organophosphate compounds--paraoxon (diethyl-p-nitrophenyl phosphate) and soman (pinacolyl methylphosphonofluoridate)--indicated a varied pattern of enzyme inhibition. These results suggested that liver microsomal carboxylesterases are involved in the metabolism of meperidine and that interference with these enzymes by organophosphate compounds may alter pharmacologic and toxicologic effects of meperidine.
Related Concept Videos
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
The direct-acting...
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Indirect-Acting Cholinergic Agonists: Mechanism of Action
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Indirect-Acting Cholinergic Agonists: Pharmacokinetics
Reversible agents containing quaternary amines, such as neostigmine and edrophonium, are not easily absorbed orally because they are...
Anticholinesterase Agents: Poisoning and Treatment
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is slower than the...
Anthelminthic Agents

