Effects of lithium on electrical activity and potassium ion distribution in the vertebrate central nervous system

Three different regions of the vertebrate central nervous system maintained in vitro (frog spinal cord, guinea pig olfactory cortex and hippocampus) have been used to investigate how Li+ influences membrane potential, membrane resistance, action potentials, synaptic potentials and the transmembrane K+-distribution of neurons and glial cells. In view of the therapeutic action of Li+ in manicdepressive disease, a special effort was made to determine the threshold concentration for the actions of Li+ on the parameters described above. It was observed that Li+ induced a membrane depolarization of both neurons and glial cells, a decrease of action potential amplitudes, a facilitation of monosynaptic excitatory postsynaptic potentials and a depression of polysynaptic reflexes. The membrane resistance of neurons was not altered. Li+ also induced an elevation of the free extracellular potassium concentration and a decrease of the free intracellular potassium concentration. Furthermore, in the presence of Li+ a slowing of the recovery of the membrane potential of neurons and glial cells, and of the extracellular potassium concentration after repetitive synaptic stimulation was observed. The threshold concentrations for the effects of Li+ were below 5 mmol/l in the frog spinal cord and below 2 mmol/l in the guinea pig olfactory cortex and hippocampus. The basic mechanism underlying the action of Li+ may be an interaction with the transport-function of the Na+/K+ pump

Cholinesterase Inhibitors for Alzheimer Disease: Multitargeting Strategy based on Anti-Alzheimer's Drugs Repositioning

International audienceIn the brain, acetylcholine (ACh) is regarded as one of the major neurotransmitters. During the advancement of Alzheimer's disease (AD) cholinergic deficits occur and this can lead to extensive cognitive dysfunction and decline. Acetylcholinesterase (AChE) remains a highly feasible target for the symptomatic improvement of AD. Acetylcholinesterase (AChE) remains a highly viable target for the symptomatic improvementin AD because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibitingperipheral AChE for myasthenia gravis had effectively proven that AChE inhibition was a reachable therapeutictarget. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for thesymptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEIs) have been continued to bedeveloped. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper,we summarize the different types of ChEIs which are under development and their respective mechanisms ofactions