Possible mechanisms involved in the presynaptic cholinotoxicity due to ethylcholine aziridinium (AF64A) in vivo.
AF64A is a toxin which can diminish irreversibly cholinergic transmission in vivo (1, 2). Disruption of neurotransmitter function in vivo is specific to the cholinergic system when AF64A is administered in nanomolar quantities (3, 4). The mechanisms involved appear to be mediated presynaptically (g). The neurochemical and behavioral consequences of AF64A administration are reminiscent of similar measures in patients with Alzheimer's disease (5, 6). Consequently, we have suggested tentatively that the AF64A treated animal may be explored as a potential animal model of this debilitating disease state (7). In this report we provide a brief overview of our recent findings using this compound in vivo, attempt to correlate these findings with those of others with similar aziridinium agnts in vitro, and propose a possible mechanism of action of AF64A in vivo, based on recent observations made in our laboratories.
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D002415:Cats; D055598:Chemical Phenomena; D002621:Chemistry; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D001388:Aziridines; D001389:Azirines; D009498:Neurotoxins; C044894:ethylcholine aziridinium; D002794:Choline; D000109:Acetylcholine