Effects Of Lithium Research Articles

Augmentation of lithium's behavioral effect by inositol uptake inhibitors.

Lithium inhibits the enzyme inositol monophosphatase and thus obstructs the enzymatic degradation of inositol triphosphate (IP3) to inositol in the phosphate-phosphoinositide (PIP) cycle. This inhibition may result in reduced availability of the second messengers IP3 and DAG that are derivates of the PIP cycle, and this action is currently a leading hypothesis regarding lithium's therapeutic and prophylactic effect in affective disorders. Inositol is also available to the cell by uptake from the intercellular matrix, and therefore it is possible that compounds that block the uptake may have lithium-like effects. To test this hypothesis, the present study evaluates the effects of two inositol uptake inhibitors, the carbohydrate L-fucose and the cyclodepsipeptide nordidemnin, in a behavioral model of pilocarpine-induced seizures known to be enhanced by lithium. We tested the possibility that L-fucose produces lithium-like effects, or that L-fucose or nordidemnin augment lithium's behavioral effects. Results indicate that acute ICV treatment with L-fucose did not by itself have a lithium-like effect in the behavioral model, but significantly augmented lithium's effect when combined with lithium treatment. Nordidemnin treatment showed similar effects. The results suggest that when inositol monophosphatase is inhibited by lithium, further restriction of cellular inositol availability may result in an augmentation of lithium's behavioral effects. It is possible that such manipulations may be applicable in the treatment of patients with affective disorders, especially patients who are poor responders to lithium monotherapy.

Lithium Modulates Biochemical Circadian Rhythms in Wistar Rats

We studied the effects of chronic lithium treatment on circadian rhythms of glucose, cholesterol, calcium, potassium, malondialdehyde (MDA), and lactic acid in Wistar rats. Lithium altered the peak time, range, and 24h mean of these biochemical rhythms. Peak times of the circadian rhythms of glucose, calcium, and potassium were delayed by 3h, 6h, and 6h, respectively, whereas circadian rhythms of MDA and lactic acid were advanced by 9h and 3h, respectively, in lithium-treated rats. Delays observed in our experiments would support the hypothesis that lithium's therapeutic effect is to delay overtly fast circadian rhythms. Advances of peak times owing to lithium treatment are discussed.

Lithium increases transcription factor binding to AP-1 and cyclic AMP-responsive element in cultured neurons and rat brain.

We have investigated whether lithium has effects on transcription factor binding to consensus DNA sequences of AP-1 and cyclic AMP-responsive element (CRE) in cultured rat neurons and in vivo. Treatment of rat cerebellar granule cells (CGC) with lithium chloride induced a concentration-dependent increase in AP-1 and CRE binding activities with maximal effects at therapeutically relevant concentrations of 0.5 and 1.0 mM. Time-course studies show that lithium's effects on AP-1 and CRE binding were biphasic within the first 24 h of treatment in immature CGC in culture and persistent in mature CGC, lasting as long as 7 days. These actions were concurrent with an increase in the mRNA levels of c-fos and c-jun, as well as the protein levels of c-Fos, c-Jun, and phosphorylated CRE binding protein (p-CREB). Gel supershift assays using transcription factor-specific antibodies revealed that p-CREB, Jun D, and a Fos family protein(s) are components of the AP-1 binding complex in untreated and lithium-treated CGC. Chronic dietary treatment of rats with lithium carbonate for 4 weeks also significantly increased AP-1 and CRE binding activity in the frontal cortex, hippocampus, amygdala, and cerebellum. Similar to the results obtained in CGC, p-CREB, Jun D, and Fos family proteins are present in the AP-1 binding sites in the frontal cortex and hippocampus of untreated and lithium-treated rats. Lithium-induced activation of transcription factor binding to AP-1 and CRE sites in vivo and in vitro provides a new avenue to study the mechanisms of action of lithium in the treatment of manic depressive illness.

Effects of lithium carbonate on reproductive hormones in healthy men: Relationship with body weight regulation-a pilot study

1. 1. To test the hypothesis that lithium-induced body weight gain is related to an unbalance in the reproductive hormones, lithium carbonate (900 mg/day) or placebo was administered to healthy men for 1 month. 2. 2. Body weight, skin folds and the serum levels of thyrotropic hormone, tetraiodothyroxine, prolactin, follicle-stimulating hormone, luteinizing hormone, testosterone (T 5), dehydroepiandrosterone sulfate (DHEAS), estradiol (E 2), cortisol, the ratios E 2 T 5 and T 5/DHEA-S, and blood lipids were evaluated before and during treatment. 3. 3. Body weight, skin folds, hormones and lipids serum levels were not significantly affected by the treatment with Li. These results agree with previous reports of lack of effects of 1 month-Li administration on appetite and body weight in normal male subjects (Chen et al., 1992), and question the appropriateness of studying Li-induced obesity in ealthy volunteers, given the short-term administration and low doses of Li that must be used.

Modulation of protein kinase C isozymes and substrates by lithium: The role of myo-inositol

Lithium is the most effective treatment for reducing both the frequency and severity of recurrent affective episodes, but despite extensive research, the molecular mechanisms underlying its therapeutic actions have not been fully elucidated. Signal transduction pathways are in a pivotal position in the central nervous system, able to affect the functional balance between neurotransmitter systems and have clearly been demonstrated to be targets of lithium's actions. We investigate the hypothesis that the action of chronic lithium on PKC isozymes and substrates may be secondary to its potent effect in inhibiting the recycling of inositol. Rats received lithium for 3 weeks and also myo-inositol or saline twice daily via intracerebroventricular (ICV) injections. There was a significant interaction between chronic lithium and myo-inositol administration, with the chronic ICV administration of myo-inositol attenuating lithium's effects on PKC alpha, PKC epsilon, and on pertussis toxin-catalyzed [32P]ADP-ribosylation. These results suggest that the effects of chronic lithium on signal transduction pathways may stem initially from its inhibition of inositol-1-phosphatase. Given the critical role of PKC isozymes and G proteins in modulating intracellular cross-talk between neurotransmitter systems and thereby the integrative functions of the CNS, future studies using other inhibitors of inositol monophosphatases are warranted, and offer the hope for the development of more potent and more rapidly acting mood-stabilizing drugs.

"In Vivo" Effects of Lithium Sulphate on the Turnover of Rat TissueNucleotides

The effects of lithium sulphate following acute administration to Wistar rats - in therapeutic and toxic doses - were investigated, using as markers the levels and turnover of brain, kidney and liver nucleotides. Adenine- and guanine-dependent nucleotides were assayed concomitantly, using a high- performance liquid chromatographic method. Following acute administration, lithium's effects on 3’,5’- cAMP levels were more significant at hepatic and cerebral level, in a dose-dependant manner. The effect on 3’,5’-cGMP had tissue specificity and was not dose-dependant. It might be possible that 3’,5’-cGMP is a better indicator of lithium toxicity than 3’,5’-cAMP.

Investigation of calcium-induced hydrolysis of phosphoinositides in normal and lithium-treated parathyroid cells

Lithium-induced hyperparathyroidism is characterized by a reduction in parathyroid sensitivity to changes in extracellular calcium (Ca2+). Ca(2+)-induced transmembrane signal transduction in the parathyroid cell is known to result in the hydrolysis of phosphatidylinositol bisphosphate (PIP2), generating increases in intracellular inositol phosphates, a process which is mediated by a calcium receptor. To determine if lithium's effect on parathyroid cell function is mediated by an alteration in Ca(2+)-induced hydrolysis of PIP2, inositol 4-monophosphate (IP1), and inositol 1,4,5-trisphosphate (IP3) were measured using anion-exchange chromatography in normal and lithium chloride (LiCl)-treated bovine parathyroid cells at Ca2+ concentrations varying from 0.5 mmol/L to 5.0 mmol/L. IP1 and IP3 concentrations were determined in terms of percent control, defined as the IP1 or IP3 concentration at an [Ca2+] of 0.5 mmol/L. Increases in [IP1]/10(6) cells (mean +/- standard error of the mean [SEM]) in response to progressive increases in Ca2+ from 0.5 mmol/L to 5.0 mmol/L varied from 825 +/- 228 to 4,474 +/- 382 in control cells versus 1,139 +/- 243 to 4,689 +/- 630 in cells pretreated with LiCl (P > 0.05). The increases in [IP3]/10(6) cells (mean +/- SEM) in response to increases in Ca2+ from 0.5 mmol/L to 5.0 mmol/L, varied from 146 +/- 14 to 385 +/- 35 in control cells versus 134 +/- 16 to 327 +/- 55 in cells pretreated with LiCl (P > 0.05). Our results demonstrate that LiCl does not effect Ca(2+)-induced hydrolysis of PIP2, suggesting that the desensitizing effect of LiCl on the parathyroid cell is not the result of a Ca2+ receptor-mediated phenomenon.

Genetic Studies in Affective Disorders

BASIC METHODS, CURRENT DIRECTIONS, AND CRITICAL RESEARCH ISSUES IN LINKAGE STUDIES: Genetic Epidemiology of Mood Disorders Diagnostic Issues in Pedigree Assessment Basic Principles in Linkage Analysis An Epidemiologic and Genetic Study of Affective Disorders Among the Old Order Amish Genetic Linkage Studies in Psychiatry Molecular Genetic Studies in Affective Illness CLINICAL ASPECTS OF THE GENETIC STUDIES: The Family Psychoeducational Approach Genetic Counselling Issues in Affective Disorders ANIMAL MODELS AND IN VITRO SYSTEMS: FUTURE DIRECTIONS: Animal Models in the Study of Genetic Factors in Human Psychopathology Lithium's Effect on Gene Expression.

Regulation of endogenous ADP-ribosylation by acute and chronic lithium in rat brain.

In the present study, we investigated the effects of lithium on endogenous ADP-ribosylation in rat brain. It was found that addition of lithium in vitro inhibits endogenous ADP-ribosylation activity in extracts of frontal cortex at therapeutically relevant concentrations. Inhibition is observed at concentrations as low as 0.3 mM and is maximal at 1 mM when 50% inhibition is obtained. A similar degree of inhibition of endogenous ADP-ribosylation was observed for all substrate proteins identified, including Gs alpha, suggesting that lithium's effect may be achieved at the level of ADP-ribosyltransferases and not specific substrate proteins. In contrast to lithium, chloride salts of sodium and potassium do not alter endogenous ADP-ribosylation activity in frontal cortex. To assess the possible in vivo relevance of this in vitro action of lithium, we studied the effect of chronic lithium administration on levels of endogenous ADP-ribosylation in frontal cortex. It was found that chronic lithium treatment, in contrast to the inhibitory effect of the drug in vitro, produced a > 35% increase in endogenous ADP-ribosylation activity. A similar degree of increase was observed for all of the substrate proteins identified. These novel findings raise the possibility that certain endogenous ADP-ribosyltransferases are among the acute targets of lithium in the brain and that adaptations in these enzymes may be part of the mechanisms underlying lithium's long-term effects on brain function.

In vitro effect of lithium carbonate on cerebellar nuclei

In vitro effect of lithium carbonate on cerebellar nuclei

Lithium and body weight gain.

Weight gain is an undesirable side-effect of long-term lithium administration which notably interferes with treatment compliance. The mechanisms of this weight gain remain unclear, making its management in patients difficult. In this paper, studies describing the features of this weight gain in patients and in rats treated with chronic lithium administration are reviewed. The effects of lithium on body weight differ between patients and rats in a number of ways, including the observation that excessive weight gain is observed in both male and female patients, but only in female rats. Nevertheless, an animal model of lithium-induced weight gain may be able to provide useful insights into some of the specific mechanisms involved, particularly those related to interactions with gonadal steroid function. We discuss the effects of lithium on the endocrine system, neurotransmitters, metabolism, electrolyte regulation, and feeding behavior, which might underlie lithium's effects on body weight. Finally, suggestions for the management of weight gain in the clinical setting are presented. These include, in the long term, dietary control and physical activity and, in the short term, choosing among several drugs that have been tested either in patients or in animal models of obesity. If weight gain still cannot be controlled and treatment compliance is at risk, the mood stabilizers carbamazepine or valproic acid might be substituted for lithium treatment.

Effect of lithium carbonate on activity level and circadian period in different strains of rats

Lithium, an important pharmacological agent for the treatment of manic-depressive illness in humans, is known to lengthen the circadian period in a number of different species. Recent experiments, on the other hand, suggest that pharmacological agents may affect the circadian system indirectly through an increase or decrease of activity. To explore the interaction between pharmacological and activity effects on the circadian system, lithium was administered chronically to three different strains of rats (ACI, BH, and LEW) while wheel-running activity was studied quantitatively. Two of these inbred strains (BH and LEW) show profound abnormalities in their circadian activity rhythms, namely, a reduced overall level of activity and bimodal or multimodal activity patterns. Wheel-running activity was monitored for 4 weeks under baseline conditions, followed by 3 weeks with lithium treatment (0.3% Li 2CO 3 administered with food) and 4 weeks with normal food. Treatment with lithium (average intake per day = 3.6 ± 0.2 mg) consistently decreased both the overall level and the circadian amplitute of the activity rhythm. The free-running period τ was slightly lengthened during lithium treatment, while the most dramatic effect on period was observed after lithium withdrawal. Correlation analysis, however, revealed only a small negative correlation between activity level and period length, which proved significantly only for animals of the ACI strain. Our data support the traditional interpretation that lithium lengthens circadian period by a direct pharmacological effect on the circadian pacemaker rather than through indirect effects of activity feedback.

Inositol Modulates In Vivo Effects Of Lithium In Rats

Lithium inhibits inositol monophosphatase of the phosphoinositide (PI) pathway, an effect which was suggested to be responsible for lithium's therapeutic action (Berridge et al, 1982). Lithium reduced inositol levels in rat brain following some treatment regimens and supplemental inositol reversed some of lithium's effects, including seizures resulting from lithium potentiating the response to cholinergic agonists (Tricklebank et al, 1991; Kofman et al, 1993). We used EEG measurements in rats to determine the effect of inositol on seizures induced by pilocarpine (30 mg/kg, sc) following pretreatment with acute (3 mmol/kg, ip, 20 hrs) or chronic (4 weeks) lithium. Myo-inositol (0-55 mmole, icv) dose-dependently attentuated lithium plus pilocarpine seizures when an acute but not a chronic lithium treatment was used. Epi-inositol, which is not utilized for PI synthesis blocked acute lithium and pilocarpine-induced seizures in 50% of tested rats. Similarly to its effect on muscarinic agonists, lithium increased the response to DOI, a selective 5-HT2/5-TH1C (PI-linked) agonist (Williams and Jope, 1994). While R-(-)DOI (8 mg/kg, ip) alone was not convulsive, lithium plus DOI evoked seizures. In some rats tested, myo-inositol blocked the effect of lithium on DOI-induced seizures.

Electrocardiographic changes of sinus bradycardia and sinus node dysfunction among patients with therapeutic levels of lithium

AbstractWe present 3 new cases of patients with mood disorders taking lithium in therapeutic doses. Each subject developed sinus node dysfunction manifested primarily as sinus bradycardia. We combine our 3 cases with 13 others from the literature to define the study population. Our findings, conclusions, and recommendations form the body of this report.When bradycardia develops and/or patients develop cardiovascular symptoms or signs, we recommend cardiologic consultation and consideration of Holter monitor recording. Psychiatrists treating patients with lithium should have a low threshold to seek cardiologic evaluation when questions about lithium's effect on the cardiovascular system arise. Depression 2:226–231 (1994/1995). © 1995 Wiley‐Liss, Inc.

Lithium decreases membrane-associated protein kinase C in hippocampus: selectivity for the alpha isozyme.

We investigated the effects of lithium on alterations in the amount and distribution of protein kinase C (PKC) in discrete areas of rat brain by using [3H]phorbol 12,13-dibutyrate quantitative autoradiography as well as western blotting. Chronic administration of lithium resulted in a significant decrease in membrane-associated PKC in several hippocampal structures, most notably the subiculum and the CA1 region. In contrast, only modest changes in [3H]phorbol 12,13-dibutyrate binding were observed in the various other cortical and subcortical structures examined. Immunoblotting using monoclonal anti-PKC antibodies revealed an isozyme-specific 30% decrease in hippocampal membrane-associated PKC alpha, in the absence of any changes in the labeling of either the beta (I/II) or gamma isozymes. These changes were observed only after chronic (4 week) treatment with lithium, and not after acute (5 days) treatment, suggesting potential clinical relevance. Given the critical role of PKC in regulating neuronal signal transduction, lithium's effects on PKC in the limbic system represent an attractive molecular mechanism for its efficacy in treating both poles of manic-depressive illness. In addition, the decreased hippocampal membrane-associated PKC observed in the present study offers a possible explanation for lithium-induced memory impairment.

Mechanism of lithium lethality in rats

Lithium inhibits inositol monophosphatase and thereby lowers inositol levels and raises inositol-1-phosphate levels. Many of lithium's biological effects are reversible by inositol replacement. However, lethality caused by high dose lithium was not found to be reversible by intracerebroventricular inositol in various dosages or schedules. Moreover, inositol-1-phosphate, given alone or in the presence of sublethal Li doses to inhibit its degradation, did not show toxic or lethal effects. Therefore inositol depletion or inositol-1-phosphate accumulation are probably not related to lithium lethality.

Luminescence and radiation effects in lithium triborate crystals

LUMINESCENCE AND RADIATION EFFECTS IN LITHIUM TRIBORATE CRYSTALS V. A. Maslov, I. N. Ogorodnikov, L. A. Ol'khovaya, I. N. Antsygin, V. Yu. Ivanov, A. V. Kruzhalov, and A. Yu. Kuznetsov UDC 535.37 In recent years the advent of new nonlinear optical media based on monocrystals of wide-band dielectrics has promoted the development of laser systems with a high radiation density. Their successful use depends, in particular, on resolving the problem of radiation-optical stability under extreme radiation conditions. It is a known fact that the formation of defects due to laser radiation worsens the nonlinear properties of crystals. These processes are rather complicated and are caused by the great number of primary events of formation and evolution of elementary point defects. Even for the best known and most widely used optical media no clear knowledge exists so far on this issue. On the other hand, the present-day level of development of laser technology dictates a search for new highly effective and radiation-resistant nonlinear crystalline media. Thus in late 1980s for the first time bulk crystals of lithium triborate LiB30 5 (LBO) were been synthesized [1-3], which surpass known crystals in threshold optical damage (a 4.1-fold increase in KTP, a 2.25-fold increase in KDP) at comparable nonlinear coefficients. This has placed LBO crystals among highly effective converters of laser radiation, in particular, of the radiation of A12Oa:Ti- lasers [4, 5 ]. By now the main physicochemical [1-3] and nonlinear [4, 5] properties of LBO crystals are studied; however data on radiation-induced defects and their properties are still absent. The appearance of bulk LBO monocrystals and ever-increasing interest in them have necessitated research studies along this line. The present work is devoted to investigation of the radiation defects, recombination processes, and spectral- luminescent properties of LBO crystals. LBO monocrystals of optical quality were grown by the modified solution-melt method with seed pulling in platinum crucibles in one- and two-zone furnaces. To increase the viscosity of the mett, Li2MoO 4 was added to the system Li20-B20 3 [6, 7 ]. Crystals were grown in the temperature range 384-810 ~ with seeding orientations {001} and {110} and the rotational speed of the seeding did not exceed 10 rpm. The mean size of the grown crystals amounted to 50 “ 40 “ 25 mm. LBO crystals were identified by x-ray analysis. The main crystallographic parameters of LBO were consistent with those in [8 ]. The luminescence of LBO crystals and its kinetics were investigated using an automated setup intended for analysis of the radiative-optical properties of solids (an MDR-2 monochromator, an FEU-106 photomultiplier tube operating in a regime of counting photons) [9 ] upon excitation by x-radiation (a URS-55 unit, Cu-anticathode, U = 40 kV, I = 10 mA) or by an electron beam (an MIRA-2D device, I = 1 A.cm -2, Zpuls e -- 10 nsec). Thermoactivation studies within the temperature range 77-600 K of practical importance were conducted using an automated unit [10 ] with x-radiation excitation of crystals. EPR spectra were measured in a modified X-band radiospectrometer RE- 1302 at two fixed temperatures (77 and 290 K). As an excitation source, use was made of a URS-55 x-ray unit and a RADAN-600 pulsed electron accelerator. The spectral-luminescent measurements showed that LBO crystals at 300 K, unlike other nonlinear crystals (e.g., KTP, KDP), show marked shortwave luminescence upon excitation by corpuscular and x-radiation. For example, the spectrum of x-ray luminescence is represented by a wide band with a peak at 4.2 eV and a weak shoulder at 3.4 eV (Fig. 1). The main band is elementary and well approximated by a Gaussian function (the halfheight line Ural Polytechnic Institute, Ekaterinburg Institute of General Physics, Russian Academy of Sciences, Moscow. Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 59, Nos. 3-4, pp. 293-298, September-October, 1993. Original article submitted December 25, 1992.

Advances in therapy for hairy cell leukemia. A review.

Hairy cell leukemia (HCL) is a chronic B-cell malignancy, typically seen in middle-aged men, characterized by pancytopenia, splenomegaly, immunologic abnormalities, and morphologically typical neoplastic mononuclear cells in the blood, bone marrow, liver, spleen, and other tissues. Diagnosis is confirmed by demonstration of hairy cells in biopsy specimens from the bone marrow or spleen or in peripheral blood. The natural history of this lymphoproliferative disorder varies. Patients may die early during the initial phase of therapy; others may require no therapy; and for some, splenectomy alone, without further treatment, may suffice for many years. Recently, the nucleosides pentostatin (2'-deoxycoformycin) (DCF) and 2'-chlorodeoxyadenosine (2-CdA) have been shown to produce greater numbers of durable complete remissions with curative potential in patients with HCL. The treatment options, with emphasis on major therapeutic advances with alpha-interferon, DCF, and 2-CdA, are reviewed in this article. Studies on HCL published from 1958 to 1992 were reviewed using the Cancerline and Medline retrieval systems and other bibliographies. Management of HCL has changed in the last decade as a result of three new effective agents: alpha-interferon DCF, and 2-CdA. DCF has produced an overall response rate of 86% and a complete remission rate of 62%. 2-CdA has yielded an overall response rate of 95% and a complete remission rate of 82%. Alpha-interferon has given an overall response rate of 82% and a complete remission rate of 8%. Other agents with limited activities include chlorambucil, cyclophosphamide, cytarabine, vincristine, doxorubicin, and zorubicin hydrochloride. The effects of lithium carbonate, immunotherapy, splenic irradiation, androgens, and leukaphoresis are minimal and transient. Modern management of HCL with 2-CdA and DCF is now potentially curative rather than palliative in some patients; however, the optimal therapeutic approach remains uncertain. Alpha-interferon has been approved by the Food and Drug Administration as the first-line drug therapy, followed by DCF in non-responding patients. 2-CdA remains an experimental therapy, but its higher response rate and ease of administration may make it the first-line treatment of choice. Additional research into the biology of HCL and further clinical trials are needed to determine the optimal treatment strategy for this disorder. Therefore, the best therapeutic approach at the current time is to include patients with HCL in ongoing clinical trials.

Long-term biphasic effects of lithium treatment on phospholipase C-coupled m 3-muscarinic acetylcholine receptors in cultured cerebellar granule cells

We have studied the long-term effects of lithium on neuronal morphology and the functional expression of phospholipase C-coupled m 3-muscarinic acetylcholine receptors (mAChRs) in cerebellar granule cells. There was a biphasic dose-dependent effect on cell morphology following treatment with lithium for 7 days. At low concentrations (⩽2 mM), this drug elicited an increase in the number and thickness of connecting nerve fibers, and the size of neuronal aggregates. At high concentrations (5–10 mM), lithium induced a severe deterioration of cell morphology, which ultimately resulted in neuronal death. Carbachol-induced phosphoinositide (PI) turnover was similarly affected by lithium treatment with a significant potentiation at concentrations up to 2 mM and a marked inhibition at doses higher than 5 mM due to lithium-induced neurotoxicity. The biphasic effect on mAChR-mediated PI hydrolysis was associated with corresponding changes in the maximal extent of carbachol-induced inositol phosphate accumulation, and was accompanied by similar changes in [ 3 H]N- methyl-scopolamine binding to mAChRs and the levels of mRNAs for m 3-mAChR and c-Fos. The up-regulation of m 3-mAChR mRNA induced by low concentrations of lithium was associated with a down-regulation of m 3-mAChR mRNA and no change in either total RNA or β-actin mRNA. Lithium's effects on m 2- and m 3-mAChR mRNAs were time-dependent, requiring a pretreatment time of ⩾3 days. The biphasic effect was also demonstrated by the binding of [ 3H]ouabain to Na +, K +-ATPase, which was shown to be a convenient method for quantifying viable neurons. The neurotoxic effect induced by treatment with high concentrations of lithium was not prevented by known neuroprotective/neurotrophic substances such as 9-amino-tetrahydroacridine or N- methyl- d-aspartate , or the co-presence of excess myo-inositol. Since the neurotrophic influence was induced by concentrations of lithium which overlap the clinical dose range and require long-term treatment, this effect might be relevant to the efficacy of this drug in the treatment of manic-depressive illness.

完全全脳虚血後の脳障害に対する炭酸リチウムの効果に関する研究

完全全脳虚血後の脳障害に対する炭酸リチウムの効果に関する研究