Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LITHIUM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources

Potassium reduces lithium toxicity: circadian rhythm actions are maintained.

We tested whether a high potassium diet alters lithium's effects on locomotor activity rhythms to the same extent as it prevents lithium toxicity. Rats fed a standard diet containing 0.47% potassium lost weight after subcutaneous implantation of an osmotic pump delivering 1.35 mg of lithium chloride per hour, and most died or became sick within three weeks after implantation. In contrast, all rats fed a diet containing 4.1% potassium gained weight at the same rate regardless of whether they had received lithium infusions or placebo. In a second experiment, lithium administration by either diet or osmotic pump delayed wheel running rhythms, showing that lithium's central nervous system action did not depend on potassium intake or method of lithium administration. Dietary potassium supplementation may provide a useful strategy for improving the therapeutic index of lithium treatment.

Animals↗

Chemical and physiological aspects of the actions of lithium and antidepressant drugs.

The possible mechanisms underlying the anti-manic actions of lithium have been examined in a variety of interdisciplinary experiments. The possibility that lithium can regulate the sensitivity changes in dopaminergic transmission produced by chronic treatment with haloperidol has been tested. Although a modest modification of behavioral responses to the dopamine agonist apomorphine was found, there was no evidence that this action of lithium reflected alterations of the binding parameters of dopamine-related ligands. In other studies, consistent, dose-dependent increases in brain enkephalin content were found after rats consumed a specially manufactured lithium diet for 2-3 weeks. Not only were brain enkephalin levels increased after this treatment, but some signs of basal analgesic responsiveness also suggested that the elevated levels of enkephalins were functionally significant. To test the possibility that the effects of lithium may not be seen in normal rats, the effects of lithium were compared on spontaneously hypertensive and unaffected, normotensive rats of a related strain. Treatment with lithium altered blood pressure in the hypertensive strain but did not affect blood pressure in the controls. These studies suggest that multiple brain systems may be regulated by treatment with lithium but that the critical pathophysiological process may not be demonstrable in the normal rat.

Animals↗

Vesicular site of action of lithium ion in choline-calcium stimulated adrenergic nerve endings of rat heart.

Reports from this laboratory have suggested that the secretion of norepinephrine (NE) in slices of ventricle from the rat heart, incubated in a medium of choline and Ca2+ (Ch+-Ca2+) deprived of Na+, is mediated by the outward transport of NE (blocked by cocaine) from synaptic vesicles fused or attached to the axolemma. Lithium (and reserpine), block the Mg2+-ATP-stimulated uptake of NE by isolated synaptic vesicles (Slotkin, Seidler, Whitmore, Salvaggio, and Lau, 1978). Hence, a hypothesis to be tested was that lithium ions would increase secretion of NE stimulated by Ch+-Ca2+. By contrast, amines mobilized by lithium ions (or reserpine) in control nerves would be deaminated. Experiments showed that lithium-Krebs increased the excretion of [3H]deaminated metabolites of [3H]NE. A much smaller quantity of [3H]NE was released by a process that was independent of Ca2+ and weakly inhibited by cocaine. When combined with Ch+Ca2+, lithium ions, in concentrations that were known to block uptake in isolated vesicles, induced a Ca2+-dependent secretion of [3H]amines. A small quantity of [3H]deaminated metabolites was excreted. Both processes were strongly inhibited by both cocaine and desipramine. Both reserpine (Bogdanski, 1982) and lithium ions blocked the inhibitory effect of exogenous ATP (2 mM) on secretion induced by Ch+-Ca2+. This effect indicated a proximity of vesicles to the axolemma. The effects of lithium ions could be explained by the hypothesis if lithium prevented storage of [3H]NE in vesicles by blocking the Mg2+ + ATP-dependent amine pump in vesicle membranes.

Adenosine Triphosphate↗

Does lithium in vitro and ex vivo alter the release of [3H]noradrenaline from brain tissue and the sensitivity of presynaptic autoreceptors?

The effect of lithium on the release of noradrenaline (NA) was investigated in slices of the cerebral cortex and hippocampus from the rat in vitro and ex vivo. In vitro, small concentrations of lithium chloride (1 and 2 mM) failed to alter the electrically stimulated tritiated overflow from slices preincubated with [3H]NA. Larger concentrations of lithium chloride (5 and 10 mM) significantly increased the electrically evoked overflow of [3H]NA by 18-40% as well as the basal 3H efflux. The alpha 2-adrenoceptor agonist clonidine inhibited, whereas the alpha 2-adrenoceptor antagonist rauwolscine facilitated the stimulated overflow of [3H]NA. These effects were attenuated by 10 mM lithium chloride but not by 2 mM. In slices of brain obtained from rats treated for 5 weeks with lithium chloride, the electrically evoked release of [3H]NA, as well as the inhibition of release of [3H]NA, induced by the alpha 2-adrenoceptor agonist clonidine were unaltered. It is concluded that therapeutically relevant concentrations of lithium do not influence the release of NA and that the function of presynaptic alpha 2-autoreceptors is not affected by chronic treatment with lithium. The increase in release of [3H]NA by larger concentrations of lithium may be relevant to its toxic effects.

Animals↗

Effects of minocycline on accumulation of cyclic AMP in cerebral cortex of rat. A comparison with lithium.

The tetracycline minocycline and lithium have been reported to share some biochemical properties. This study was aimed at investigating the effects of minocycline and lithium in vitro on accumulation of noradrenaline-, forskolin- and calcium-(Ca2+) stimulated cyclic AMP (cAMP) in the cerebral cortex of the rat. Minocycline and lithium dose-dependently inhibited noradrenaline-stimulated formation of cAMP in slices of cortex, but only lithium inhibited the formation of cAMP induced by forskolin. In contrast to lithium, minocycline did not affect either noradrenaline- or Ca(2+)-stimulated activity of adenylate cyclase in a preparation of cortical membranes. However, in slices of cortex ouabain-induced formation of cAMP (dependent on extracellular Ca2+ and blocked by the Ca2+ channel antagonist, verapamil) was reduced both by minocycline and lithium. The present results indicate that the mechanisms of action of minocycline and lithium on the cAMP signalling system in the brain of the rat differ. Minocycline does not seem to interact directly with the adenylate cyclase, as reported for lithium. The decreased agonist-stimulated production of cAMP in intact cells, in the presence of minocycline, might be due to the ability of minocycline to chelate Ca2+ ions.

Adenylyl Cyclases↗

Lithium adverse reactions in psychiatric patients.

A brief review of the literature on the adverse reaction of lithium therapy in man is presented. This was aimed at both toxic and side effects of lithium on various organ systems of the body. Inconclusive, insufficient or conflicting data were found in several areas of possible lithium-induced toxicity, notably in lithium-associated nephrotoxicity. Results of prospective studies are needed to clarify this issue. Adverse reactions derived from continued administration of lithium salts with neuroleptic medications or with electroconvulsive therapy were also reviewed. Lithium-induced side effects on the endocrine and gastrointestinal systems were also summarized along with both dermatologic and ophthalmologic effects. The teratogenicity of lithium during pregnancy and its cardiovascular abnormalities were discussed. The target organs of lithium poisoning and their management were also presented.

Abnormalities, Drug-Induced↗

Determination of lithium in rat brain regions and synaptosomes by graphite furnace atomic absorption spectrophotometry.

A graphite furnace atomic absorption spectrophotometric method for the analysis of very low concentrations of lithium in brain tissue and subcellular fractions is described. The method has a picogram sensitivity and shows a precision value of 10.1% expressed as the per cent variation coefficient for the tissue analysis of the metal. Lithium concentration in eight regions of the rat brain and regional synaptosomal lithium contents were analyzed with the method described. Results from these determinations show that lithium is heterogeneously distributed among rat brain regions 24 hr after a single s.c. lithium administration; hypothalamus, corpus striatum and midbrain were the regions with the highest lithium accumulation. Lithium is homogeneously concentrated in the synaptosomes obtained from rat brain regions. The method proposed may be considered adequate for trace lithium analysis in pharmacological studies of the metal.

Animals↗

Lithium, red blood cell choline and clinical state. A prospective study in manic-depressive patients.

Red blood cell (RBC) choline and ergothioneine levels were measured after repeated sampling of bipolar manic-depressive patients over 11 months of lithium maintenance. In addition, blood levels were measured in healthy volunteers, newly hospitalised lithium-free patients and from patients prior to, and after, initiating lithium. RBC choline levels did not differ between normal volunteers and newly admitted lithium-free patients with either mania or depression. After 4 weeks of lithium treatment RBC choline levels increased 6-fold, whereas the levels of the closely related compound ergothioneine did not change. Significant changes in mood during lithium maintenance were not accompanied by changes in RBC choline levels. These data indicate that lithium produced a specific accumulation of choline in erythrocytes. However the increased levels appear to be unrelated to clinical state and do not distinguish lithium responders from non-responders

Adult↗

Suicides and parasuicides in a high-risk patient group on and off lithium long-term medication.

68 patients with affective disorders, and receiving lithium prophylaxis in a specialized lithium clinic were followed up for 8 years on average. Patients were selected for this study according to 2 criteria: They had been given lithium for at least 12 months, and they had attempted suicide at least once before onset of lithium prophylaxis. Outcome was analysed in terms of suicidal and parasuicidal behaviour. 55 patients took their lithium regularly, 13 discontinued or dropped the medication. One third of those patients having discontinued the medication died from suicide. Only one suicide occurred in patients with regular lithium intake and proven compliance during the last check before death. An impressive drop of parasuicides was observed in responders as well as in apparent non-responders. In total, 11 of 13 patients showed suicidal or parasuicidal behaviour 2 weeks-44 months after lithium discontinuation, which in about half of these cases took place on advice or with consent of the treating psychiatrist. It is concluded that lithium may have specific anti-suicidal properties, possibly related to its anti-aggressive effect, and that patients apparently not responding satisfactorily in terms of reduced number of episodes may still be protected against suicide or parasuicide.

Adult↗

[Hyperthyroidism after lithium withdrawal: coincidence or not?].

A 59 year-old manic-depressive woman treated with lithium for 10 years, developed hyperthyroidism three months after lithium withdrawal. The usual side effects on lithium on thyroid function include hypothyroidism and/or development of a goiter. Hyperthyroïdism occurring during lithium therapy is more rarely described. Hyperthyroidism has been exceptionally reported after lithium withdrawal, as in this case (five cases are recorded). The role of lithium in this pathology is controversial. Well-designed prospective studies are needed to clarify this question. Nevertheless, the effects of lithium on the thyroid metabolism are not always harmless and must prompt the clinicians to control the thyroid hormones before, during and after lithium therapy.

Female↗

The lithium index in a one-year follow-up.

1. In a one-year follow-up 191 patients on lithium therapy, besides their regular check-ups, were assessed on mood, side-effects and intracellular lithium. 2. The authors were not able to find a correlation between the so called lithium index (i.e. the quotient intracellular lithium/plasma lithium) and the mood score. 3. In the group of patients which used no co-medication at all during the year of the follow-up the authors also failed to find a correlation between the lithium index and some of the clinically most relevant side-effects. However, in that selected group of "only-lithium-using-patients"-only 29 in all-the authors found a remarkable stability in the index value. 4. So even if the authors, in fact, rejected the lithium index estimation as a tool in daily praxis, the authors would once again underline the interesting findings about the so-called lithium index.

Affective Disorders, Psychotic↗

Lithium attenuates hypokinesia induced by immobilization stress in rats.

1. Hypokinesia following immobilization stress in rats is attenuated by anti-depressant drugs used in the treatment of unipolar depression. Lithium has anti-depressant effects both clinically and in other animal models of depression, but the mechanism of its anti-depressant effect has not been elucidated. 2. To determine if lithium reverses immobilization-induced hypokinesia, the effects of lithium and immobilization stress were tested in a fully factorial 2 x 2 design. 3. Half the rats were fed chronic dietary lithium, while the other half ate regular chow. Half of each group were exposed to one hour immobilization, while the other half remained in their home cages until the test. Activity was measured for 20 min in an automated activity meter. 4. Stress significantly reduced activity, but a significant interaction between stress and lithium was found, indicating that lithium attenuated the effect of stress. 5. Lithium-induced attenuation of immobilization stress may serve as an animal model for the anti-depressant effects of lithium.

Analysis of Variance↗

Presence and significance of lithium in the brown shrimp, Crangon crangon (L.).

1. In female (non-ovigerous and ovigerous) brown shrimps, Crangon crangon, whole animal lithium levels are about 20% higher than in males, which indicates that lithium has a special function in the female reproductive system. 2. Decreasing lithium levels in larger males suggest that with males a substantial part of the lithium present may be passively absorbed to the exoskeleton. 3. At low temperatures internal lithium concentrations are strongly increased. In response to external salinity the internal lithium concentrations show a typical regulation pattern. The effects of temperature and salinity clarify that lithium must be involved in metabolic processes. 4. Apart from a special function in the reproductive system, lithium can probably replace other ions in their function, e.g. in regulating the activity of enzymatic processes.

Animals↗

Influence of lithium on mammary tumor growth in vivo.

The possibility that lithium ions stimulate growth of mammary tumors in vivo has been suggested by their mitogenic action in vitro on normal and neoplastic mammary epithelium [8] and their clinical use as stimulators of neutrophil production in tumor-bearing patients treated with cytotoxic drugs [14,15]. Three experiments were performed to assess this possibility. Buffalo/N female rats received a single injection of N-nitrosomethylurea (NMU) at a dose known to produce mammary carcinomas in about 50% of animals under standard conditions. Under lithium treatment, the incidence of tumors did not increase significantly. Sprague-Dawley female rats treated with a single dose of 7,12-dimethylbenz[alpha] anthracene (DMBA), but showing no mammary tumors after 4 months, received lithium in their drinking water for 3 additional months. The number of late-appearing tumors was not increased by lithium treatment. Buffalo/N females with NMU-induced tumors were castrated, and the subsequent changes in tumor volume were compared in lithium-treated and control animals. The regression-regrowth curves were not altered by lithium treatment. These results are in contrast to the growth stimulatory capacity of lithium on mammary epithelium observed in vitro [8] and indicate it is very unlikely that lithium ions have an undesirable growth stimulatory action on primary mammary carcinomas in vivo.

9,10-Dimethyl-1,2-benzanthracene↗

Mineral springs and spring fever. Lithium: fact and fantasy in psychopharmacology.

Lithium salts have been employed as medical treatment for more than two thousand years. The history of lithium in medicine reveals a strictly empiricist approach to its use which has resulted in its varying popularity as a therapeutic treatment over the past century. Much of the enthusiasm about the therapeutic use of lithium has been generated by faulty scientific process. This paper reviews the scientific errors which have surrounded the medical use of lithium in history, discusses the metaphorical use of medical terminology and the problem which is posed by the literal interpretation of such terms, and challenges the currently accepted point of view that lithium is a specific treatment for mania. The scientific errors which have resulted in the introduction of lithium as a treatment for mania are reviewed, and it is proposed that lithium treatment be viewed as the paradigm of modern psychopharmacology. The author suggests that the empiricist approach in biological psychiatry requires critical scrutiny in order to avoid tragic consequences, regarding the hazards both to patients arbittrarily exposed to lithium therapy, as well as to the scientific concept of disease as it is modified by those who wish to re-define disease, empirically, in terms of response to treatment.

Affective Symptoms↗

[Important hypercalcaemia due to hyperparathyroidism induced by lithium].

Lithium treatment, which is still extensively used in bipolar affective disorders, may give rise to hypercalcaemia induced by hyperparathyroidism. We present a patient of 50-year-old treated with lithium for 19 years for bipolar illness and who developed an important hypercalcaemia. After symptomatic treatment of the hypercalcaemia and extrarenal dialysis the clinical evolution was favorable but measurements of serum calcium and parathormon showed that he had developed hyperparathyroidism. Neck exploration was performed and parathyroid adenomas, which had been detected by scintigraphy was removed. The lithium treatment expose to many side effects. Among other biologically and clinically important effects of lithium the possible induction of hyperparathyroidism was first suggested in 1973. Since, 1973, since about forty case reports have been described. Few cross-sectional studies show a relationship of lithium to hyperparathyroidism. Unusual metabolic features are associated with hyperparathyroidism and long-term lithium treatment: low urinary calcium excretion, normal urinary cyclic AMP excretion. The mechanism probably results from lithium linking with the calcium receptor on the parathyroid and then stimulating PTH secretion. The cessation of lithium therapy does not lead to normocalocaemia and a parathyroidectomy is usually indicated.

Antimanic Agents↗

Enhancement of neuroprotection and heat shock protein induction by combined prostaglandin A1 and lithium in rodent models of focal ischemia.

Both prostaglandin A(1) (PGA(1)) and lithium have been reported to protect neurons against excitotoxic and ischemic injury. The present study was undertaken to examine the effects of lithium and PGA1 on heat shock proteins (HSP) and the growth arrest and DNA-damage-inducible gene (GADD153) and to evaluate if lithium could potentiate PGA(1)'s neuroprotective effects against cerebral ischemia. Rats were pretreated with a subcutaneous injection of lithium for 2 days and a single intracerebral ventricle administration of PGA(1) 15 min before ischemic insult. Brain ischemia was induced by a permanent middle cerebral artery occlusion. The infarct volume, motor behavior deficits and brain edema were analyzed 24 h after ischemic insult. The result showed that PGA(1) significantly reduced infarct volume, neurological deficits and brain edema. Except for neurological deficit, lithium enhanced PGA(1)'s neuroprotection. The neuroprotective effects of PGA(1) were associated with an up-regulation of cytoprotective heat shock proteins HSP70 and GRP78 in the ischemic brain hemisphere as determined by immunoblotting and immunofluorescence. The induction of HSP70 and GRP78 was enhanced by lithium. However, although the expression of GADD153 was enhanced significantly after pMCAO, it was not influenced by either PGA(1) or lithium or their combination. These studies suggest that lithium can potentiate PGA(1)'s neuroprotective effects and thus may have potential clinical value for the treatment of stroke in combination with other neuroprotective agents.

Analysis of Variance↗

A cross-sectional and a prospective study of thyroid disorders in lithium-treated patients.

BACKGROUND: The effects of lithium treatment on the thyroid gland have been demonstrated in a number of studies. Most of this research is based on cross-sectional studies and prospective studies are required to confirm these observations. METHOD: During our genetic association studies, we recruited 115 males and 159 females suffering with affective disorders who had received lithium treatment. We observed longitudinally 57 of these patients, who attended our clinic for between 1 and 7 years and had no thyroid abnormalities at baseline. We performed regular checks of thyroid antibodies, thyroid function tests and lithium levels. RESULTS: Hypo- and hyperthyroidism, including cases that developed prior to lithium treatment, were more common in women (25.8%) than in men (8.7%) and increased with age. By the age of 65, the risk in women increased to 50%. Hypothyroidism was induced by lithium in 17% women. In the prospective study, 4 out of 33 women developed hypothyroidism (an incidence of 27.4 cases per 1000 years). One woman developed thyrotoxicosis. CONCLUSIONS: The risk for hypothyroidism induced by lithium is especially increased in women over the age of 50. Women should be warned of the risks involved when offered lithium treatment. The frequency of lithium-induced thyrotoxicosis is very low.

Antipsychotic Agents↗