An Irreversible Effect of Lithium Administration to Patients

Abstract

1Lithium administration to patients leads to a pronounced inhibition (about 90%) of the choline transport system in erythrocytes. The transport system does not recover when ghosts are prepared from the erythrocytes, thereby removing intracellular as well as extracellular lithium. 2 When a patient is taken off lithium, the choline transport in erythrocytes recovers only very slowly over a period of three months, i.e. at about the same rate at which the erythrocytes that had been exposed to lithium are replaced by new cells. 3 It is concluded that therapeutic concentrations of lithium produce an irreversible inhibition of the choline transport system in human erythrocytes.

Erythrocyte choline concentrations are elevated in manic patients.

“…1). A similar specificity has been reported for the effect of Li+ on erythrocyte Cho fluxes (8,9). Further research into the significance of this finding for central nervous system function will depend upon finding a laboratory species that shares this response with humans.…”

An Excitatory Action of Iontophoretically Administered Lithium on Mammalian Central Neurones

“…In this condition, the slow onset of the effect of Li+ could be attributable to a slow accumulation of Li+ within the terminals, limited by the low plasma levels that can be tolerated. However, the occurrence of a relatively non-reversible mechanism (Lingsch & Martin, 1976) which does not depend on relatively simple ionic disturbances cannot be discounted in the explanation both of the therapeutic effect of Li+ and the postulated facilitation of transmitter release.…”

“…Our interest in a possible link between the therapeutic action of lithium and cholinergic mechanisms arose from observations by Lee, Lingsch, Lyle & Martin (1974) and Lingsch & Martin (1976) that choline uptake into human erythrocytes is greatly reduced in lithium-treated patients and that the effect seemed to be irreversible and independent of the presence of lithium at the time of measurement. It seemed possible that a similar process occurring in central cholinergic terminals might reduce acetylcholine (ACh) synthesis, thereby impairing cholinergic transmission.…”

Lithium, membranes, and manic-depressive illness

“…Choline transport in RBC is irreversibly reduced 90% after prolonged Li + treatment (Lee et al, 1974;Lingsch & Martin, 1976). In vitro exposure to Li + also reduces choline transport but only to 40% of control levels (Lingsch & Martin, 1976).…”

“…In vitro exposure to Li + also reduces choline transport but only to 40% of control levels (Lingsch & Martin, 1976). As an initial step to investigate further the RBC choline transport system, endogenous levels of choline in plasma and RBC were measured in control subjects and in Li+-treated patients.…”