PMID: 3748277Jul 1, 1986Paper

Hemicholinium mustard derivatives: preliminary assessment of cholinergic neurotoxicity

Neurochemical Research
P C TagariA C Cuello

Abstract

We have attempted to design novel neurotoxins based on the use of hemicholinium derivatives. Three compounds were tested for their neurochemical effects on cholinergic, gabaergic and catecholaminergic markers in the hippocampus, striatum and cortex following intracerebroventricular administration. The effects were compared with those of the non-specific alkylating agent (nitrogen mustard) and the previously reported ethylcholine mustard aziridinium ion (AF 64A). The results indicate that only one of these derivatives (HcM-9) exhibits comparable neurotoxic effects on cholinergic markers with a similar pattern of specificity to that of AF 64A. In addition, HcM-9 showed less overall toxicity, this being reflected in a higher survival rate. The present results indicate that hemicholinium derivatives could be good substrates for further molecular modifications, thus a step towards the design of a more specific cholinergic neurotoxin.

References

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Citations

Jan 1, 1989·Neurochemistry International·D MaysingerA C Cuello
May 11, 1992·Annals of the New York Academy of Sciences·I Hanin
Oct 15, 1986·Biochemical Pharmacology·D MaysingerC Cuello

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