title: Prevention of physostigmine-induced lethality by the opioid analgesic meptazinol in the mouse.
abstract: The prophylactic action of meptazinol against physostigmine- and neostigmine-induced lethality was evaluated in mice. Meptazinol proved to be effective against physostigmine (1 mg kg-1 i.p.), but not against neostigmine (0.5 mg kg-1 i.p.). The antagonism by meptazinol of physostigmine-induced poisoning was maximal when the drug was administered 15 min before physostigmine. Under these conditions the ED50 (95% confidence limits) of meptazinol was 24 (22.0-26.1) mg kg-1 s.c. A 30 mg kg-1 dose of the drug prevented lethality in 89% of the animals. The action of meptazinol was not antagonized by naloxone hydrochloride (2 mg kg-1 i.p.), injected 10 min before meptazinol. Pretreatment of mice with 30 mg kg-1 meptazinol 15 min before physostigmine (1 mg kg-1) poisoning increased brain acetylcholinesterase (AChE) activity on average, from 8 to 31% of control values. The protection of cholinesterases against physostigmine- and neostigmine-induced inactivation was demonstrated in vitro directly on purified preparations of the enzymes using a dilution method. The ED50 values (95% confidence limits) for the protective effect of meptazinol of electric eel AChE against 1 and 3 microM physostigmine and 1 microM neostigmine were 2.6 (1.4-4.9), 9.5 (5-18) and 3 (1.6-5.7) microM, respectively, while for protection of horse serum butyrylcholinesterase (BuChE) against the same inhibitors, the ED50 values were 12 (5.4-26.4), 42 (27-65.1) and 8 (3.6-17.6) microM, respectively. It is suggested that prevention of physostigmine-induced lethality by meptazinol is a consequence of its protective action on AChE in the central nervous system.
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000378:metabolism; D004593:Electrophorus; D006736:Horses; D066298:In Vitro Techniques; D008297:Male; D008621:Meptazinol / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009388:Neostigmine / Q000037:antagonists & inhibitors; D010830:Physostigmine / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D001381:Azepines; D008621:Meptazinol; D009388:Neostigmine; D010830:Physostigmine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase