Potter_1989_Neurochem.Int_14_433

Reference

Title : Effects of LF-14, THA and physostigmine in rat hippocampus and cerebral cortex - Potter_1989_Neurochem.Int_14_433
Author(s) : Potter PE , Nitta S , Chaudhry I , Lalezari I , Goldiner P , Foldes FF
Ref : Neurochem Int , 14 :433 , 1989
Abstract :

The effects of physostigmine, tetrahydroaminoacridine (THA) and LF-14 [3,3-dimethyl-1(4- amino-3-pyridyl)urea], a 3,4-diaminopyridine derivative, were compared on inhibition of acetyl- cholinesterase (AChE) activity, and release of [(3)H]acetylcholine (ACh) from rat brain cortical and hippocampal slices. All three compounds caused a concentration dependent inhibition of AChE, with an order of potency physostigmine > THA >LF-14. The electrically stimulated release of ACh from hippocampal and cortical slices was decreased by 10(?5)M physostigmine, although the effect was significant only in cortex. THA (5 x 10(5)M) caused a slight, but not significant, decrease in ACh release from both tissues. In contrast, LF-14 (5 x 10(?5) M) caused an approx. 3-fold enhancement of stimulated release. When AChE was inhibited by prior addition of physostigmine, THA caused only a slight enhancement of ACh release, whereas LF-14 greatly increased release. ACh release was also reduced by stimulation of presynaptic muscarinic receptors with oxotremorine. In this case, THA had no effect on ACh release, while LF-14 was able to reverse the inhibition. This study suggests that LF-14 acts to promote ACh release through blocking K(+) channels, and has a less potent AChE inhibitory effect. It is possible that a compound like LF-14 could be useful in treating diseases of cholinergic dysfunction such as Alzheimer's disease, by both promoting the release of ACh and inhibiting its breakdown.

PubMedSearch : Potter_1989_Neurochem.Int_14_433
PubMedID: 20504446

Related information

Inhibitor LF-14
Chemical LF-14    3,4-Diaminopyridine

Citations formats

Potter PE, Nitta S, Chaudhry I, Lalezari I, Goldiner P, Foldes FF (1989)
Effects of LF-14, THA and physostigmine in rat hippocampus and cerebral cortex
Neurochem Int 14 :433

Potter PE, Nitta S, Chaudhry I, Lalezari I, Goldiner P, Foldes FF (1989)
Neurochem Int 14 :433