Antagonism of acute physostigmine and neostigmine toxicity in mice by hemicholinium-3.
Hemicholinium-3 (HC-3) was administered intraperitoneally to mice concurrently with the intraperitoneal administration of physostigmine or neostigmine. HC-3 increased the LD50 values for both physostigmine and neostigmine but did not alter the effect on brain ACh levels produced by these agents. Since HC-3 does not cross the blood brain barrier after intraperitoneal administration, the antidoting action of HC-3 is peripherally mediated and does not solely involve an inhibition of ACh synthesis. The increase in brain acetylcholine caused by neostigmine was related to a reduction in acetylcholinesterase activity, providing evidence that intraperitoneally administered neostigmine crosses the blood-brain barrier.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D006426:Hemicholinium 3 / Q000494:pharmacology*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009388:Neostigmine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010830:Physostigmine / Q000037:antagonists & inhibitors* / Q000633:toxicity
D006426:Hemicholinium 3; D009388:Neostigmine; D010830:Physostigmine; D000109:Acetylcholine