Central cholinergic activity in aluminum-induced neurofibrillary degeneration.

Choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities were measured in spinal cord homogenates from rabbits with aluminum-induced neurofibrillary degeneration and a group of saline-treated, age-matched controls. All aluminum-treated animals showed neurofibrillary changes in the spinal cord, but CAT and AChE activities were not significantly different from levels in control animals. These results are at variance with the greatly reduced activity of these enzymes observed in Alzheimer disease and senile dementia of the Alzheimer type.

Regional distribution of choline acetyltransferase and acetylcholinesterase in rabbit brain.

Regional distribution of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) in seventeen regions of the rabbit CNS has been determined by means of the cation exchange radiometric method. A significant correlation has been found between the activities of AChE and CAT which allows computation of their potencies. A comparison between activities of the cholinergic enzymes in the human and rabbit brain has been discussed.

On some derivatives of ferrocene, novel acetylcholinesterase inhibitors.

Eight novel methylcarbamates, derivates of ferrocenylketoximes and aldoximes, and ferrocenyl-p-hydroxyphenylaldimine were prepared. They are the first carbamates in the field of ferrocene derivatives. Their anticholinesterase activity was tested and found to fall in the range of 10(-4) through 10(-6) M (I50). The correlation between the activity of the compounds and the kind of substituents grafted on the methylene carbon atom is discussed.

Application of the charge-transfer constant for correlation of acetylcholinesterase affinity reciprocals vs. physico-chemical properties of aromatic inhibitors.

Some properties of the charge-transfer constant (CT) have been described. The constant in association with the Hansch coefficient (pi, hydrophobic coefficient) for 32 aromatics was applied for the correlation with reciprocals of their acetylcholinesterase affinities (KD). The investigated aromatics constituted p- and m-substituted phenyl methylcarbamates, carbaryl (1-naphthyl methylcarbamate), p-substituted phenylmethyl methylcarbamates, and various aromatics without the carbamyl group, the dependencies found for the following relations: KD vs. (CT + sigma delta CT), where CT is the charge-transfer constant for a whole aromatic system and delta CT refers to effects of substitutents upon it; KD vs. sigma pi; KD vs. (CT + sigma delta CT) + sigma pi; and KD vs. [(CT + sigma delta CT), sigma pi] were characterized by the correlation coefficients 0.72, 0.82, 0.92, and 0.93 respectively.

The charge-transfer constant. A new substituent constant for structure-activity relationships.

A new, versatile constant accounting for the pi-complex formation ability of aromatic systems is proposed. The constant is derived from charge-transfer complex data of aromatic species (charge-transfer constant, CT). The applicability of CT in structure-reactivity relations is demonstrated. It is shown that the affinity of various inhibitors (32) and acetylcholinesterase is a function of CT and pi (Hansch hydrophobicity constant).