Reversible inhibition of acetylcholinesterase by eseroline, an opioid agonist structurally related to physostigmine (eserine) and morphine.
The action of eseroline--(3aS,8aR)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indo l-5-ol--salicylate was tested on preparations of ChE from different sources and on the longitudinal muscle of guinea-pig ileum. While eseroline is eseroline is extremely weak-acting on horse serum BuChE (Ki = 208 +/- 42 microM), it is a rather strong competitive inhibitor of AChE's, its Ki being 0.15 +/- 0.08 microM, 0.22 +/- 0.10 microM and 0.61 +/- 0.12 microM in electric eel, human RBC and rat brain, respectively. Eseroline inhibitory action in AChE in independent of the duration of pre-incubation and appears fully developed in less than 15 sec. This action is also rapidly reversible; after pre-incubation followed by dilution, maximum enzymic activity is regained within 15 sec. The electrically-evoked contractions of the longitudinal strip were inhibited by concentrations of eseroline in the range 0.2-15 microM, while they were increased by concentrations over 20 microM. In the same preparation, without electrical stimulation, but in the presence of naloxone, eseroline induced contractions at concentrations higher than 5 microM. This effect was antagonized by atropine. The inhibitory activity of eseroline parallels, as regards selectivity, potency and kinetics, that of the phenolic anticurare agent edrophonium, while it differs markedly from that of physostigmine.
D000818:Animals; D002800:Cholinesterase Inhibitors; D004558:Electric Stimulation; D004593:Electrophorus; D006168:Guinea Pigs; D006736:Horses; D006801:Humans; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D009022:Morphine Derivatives; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010830:Physostigmine / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D007211:Indoles; D009022:Morphine Derivatives; D010830:Physostigmine; C022594:eseroline