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PubMedDate not supplied

[Lithium oxybutyrate correction of the circadian pattern of reserpine-induced depression].

Lithium oxybutyrate was studied for effects on the circadian pattern of reserpine-induced depression ("open field") in relation to the time of the drug use. Reserpine given in a single dose of 0.75 mg/kg caused a reduction of diurnal frequencies, inversion of rhythm acrophases, decrease in their mesors and amplitudes. Lithium oxybutyrate given after rhythm acrophases in reserpine-treated animals recovered the lost 24-hour harmonics phase relations between them, but when used before acrophases it did not only fail to prevent the animals from the exhausting action of reserpine, but aggravated the course of depression.

Animals↗
PubMedDate not supplied

[The effect of lithium oxybutyrate on the development of the fetus and progeny in alcoholic intoxication of male rats].

The effect of lithium hydroxybutyrate on the development of the fetus and offsprings was studied on a model of alcohol intoxication of male rats. Under such conditions lithium hydroxybutyrate relieved completely the negative action of alcohol on the reproductive function, according to all parameters. The learning ability of the offsprings and their behavioral disorders in a stress situation caused by alcohol were normalized. Two-week administration of 100 mg/kg lithium hydroxybutyrate had no negative effect on the embryonal and postnatal development of the offsprings.

Aging↗
PubMed1982

Flavor-illness aversions: gustatory neocortex ablations disrupt taste but not taste-potentiated odor cues.

Two experiments evaluated the contribution of the gustatory neocortex (GN) to the potentiation of odor by taste during illness-induced aversions in rats. In Experiment 1, rats lacking GN and control rats were given an odor, a taste, or an odor-taste compound cue followed by intragastric gavage of lithium chloride. Prior to conditioning, neophobia for flavored solutions was absent in rats with GN lesions. After pairing with LiCl, GN rats developed normal conditioned odor aversions (Experiment 1B), whereas conditioned taste aversions were attenuated (Experiment 1A) or totally blocked (Experiment 1B). Potentiation of odor by taste after compound conditioning was evident in both control and GN rats, although GN lesions attenuated the effect slightly in Experiment 1B. In Experiment 2, normal rats were given compound conditioning to induce potentiated odor aversions and then given GN lesions prior to tests with the odor and taste components. Taste aversion retention was disrupted totally by GN ablation; potentiated odor aversions were retained by both groups, although the GN group extinguished faster. Gustatory neocortex ablations produced differential effects on odor and taste, disrupting taste memorial and associative processes but leaving odor conditioning and the potentiation of odor by taste processes relatively unaffected. Integrity of the GN apparently is not necessary for the acquisition or retention of potentiation odor aversions.

Animals↗
PubMed1980

Potentiation rather than overshadowing in flavor-aversion learning: an analysis in terms of within-compound associations.

Five experiments investigated the development of aversions to stimuli with strong odor components. Those odors were presented simultaneously with tastes are followed by lithium chloride. Contrary to expectations derived from previous investigations of compound conditioning, the presence of a taste stimulus at the time of conditioning was found to potentiate rather than overshadow the resulting odor aversions. Explanations in terms of either the taste's unconditioned aversiveness or nonassociative effects were found to be inadequate. An alternative interpretation attributing potentiation to the summed effects of within-compound odor-taste associations and odor-unconditioned stimulus associations was suggested. In agreement with such an interpretation, evidence of odor-taste associations was found in this situation. Furthermore, continued aversiveness of the taste was necessary for potentiation of the odor aversion to occur. An account of potentiation in terms of within-compound associations makes the phenomenon compatible with modern theories of Pavlovian associations.

Animals↗
PubMed1994

Determination of beta-isomerized aspartic acid as the corresponding alcohol.

The age-related formation of succinimides in proteins, through spontaneous deamidation of asparagine, and through cyclization of aspartic acid, is thought to be followed by the hydrolysis of the succinimide ring, yielding a mixture of "normal" aspartic acid sites and beta-isomerized aspartic acid sites (isoaspartic acid). The chemical reduction of an isoaspartyl site to the corresponding amino acid alcohol, isohomoserine, has now been investigated as a general approach to measuring the accumulation of isomerized residues in aging proteins. The methods employed were based on conditions previously found to be successful in reducing protein aspartic acid to homoserine. Borane was employed as the reducing agent, and was found to produce the expected amino acid alcohols in reactions with model peptides. In addition, amino acid analysis revealed a complex pattern of unknown products of these reduction reactions, some of which were also evident when a much stronger reducing agent, lithium aluminum hydride, was used. The correlation of some of these side-products with the isomerization of the peptide suggests, unexpectedly, that the reactivity of reducing agents toward aspartyl residues and perhaps other sites in the peptide may be influenced by steric factors related to aspartyl isomerization. The borane reduction method was also applied to proteins. No detectable isohomoserine was formed either in ovalbumin, a model aged protein, or in human lens proteins of advanced age, with conditions that fully reduced normal aspartyl residues to homoserine. These tests thus indicate that the percentage of aspartic acid in the isomerized form in these proteins is below the limit of detectability (below approximately 5%). These results complement previous experimental results that have indicated a low bulk isoaspartyl content in most natural proteins.

Aluminum Compounds↗
PubMed1980

Analgesic narcotic antagonists. 4. 7-Methyl-N-(cycloalkylmethyl)-3-hydroxymorphinan-6-ones and -isomorphinan-6-ones.

3,6-Dimethoxy-7 beta, 17-dimethyl-4-hydroxy-5,6,8,14-tetradehydromorphinan (2) was converted to the 4-deoxy compound 4 and hydrolyzed to a mixture of the B/C-cis (C series) and B/C-trans (T series) isomers of 7,8-didehydromorphinan-6-one, 5. Hydrogenation of the separated isomers gave 7-methyl-6-oxo derivatives 6a. 7,8-Dimethyl-(6b) or 7-methyl-8-ethylmorphinan-6-one (6c) was prepared by reaction of 5 with lithium organocuprates. The analgesic N-methyl compounds 6 were converted to 17-(cyclopropylmethyl) or 17-(cyclobutylmethyl) derivatives 10--13. Some of these compounds had mixed profiles of narcotic agonist-antagonist effects. Studies with drug-dependent monkeys indicated that several of these compounds with an analgesic-antagonist ratio of less than 0.4 substitute for morphine.

Analgesics↗
PubMed2007

Quantitative data on the effects of alkyl substituents and Li-O and Li-N chelation on the stability of secondary alpha-oxy-organolithium compounds.

A DeltaG(eq) stability scale of secondary alpha-oxy-organolithium compounds was established from measurements of tin-lithium exchange equilibria in THF, and the quantitative effects of substituents at the anionic center on carbanion stability are presented. A new lead-lithium exchange equilibrium reaction was also investigated and shown to be a very useful alternative for the determination of the relative stability of the more sterically hindered organolithium compounds. Alkyl groups adversely affect the stability of organolithium compounds when attached to the carbon bearing the negative charge, but the extent of this effect is highly dependent on the nature of the rest of the substituents attached to the anionic center. Quantitative data on the stabilization imparted to organolithium compounds by Li-O and Li-N chelation have been determined for a variety of systems. The formation of four- and five-membered chelate rings leads to a considerable stabilization of the organolithium compound, while chelation through the formation of six-membered rings affords no extra stabilization to this type of organometallics. Multinuclear NMR experiments carried out on several alpha-oxy-organolithium compounds to determine their aggregation state are supportive of these species being monomers in THF solution.

Journal Article↗
PubMed1998

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.

Animals↗
PubMed2002

Conformational control of flexible molecules: design and synthesis of novel chiral 1,5-diaza-cis-decalins.

Control of the conformational equilibria of 1,5-diaza-cis-decalins, a new class of chiral diamine ligands, has been investigated. Chiral 2,6- and 3,7-substituted derivatives of 1,5-diaza-cis-decalins were designed to stabilize the conformational form needed to chelate a lithium. These derivatives were synthesized in optically pure form starting from 1,5-diaza-cis-decalin. Due to the rigid and conformationally well-defined nature of these compounds, the potential of these compounds as chiral diamine ligands was investigated. Asymmetric lithiation-substitution reactions of N-Boc-pyrrolidine and N,N-diisopropyl-o-ethylbenzamide were performed using these ligands and up to 60% ee was obtained. For the latter substrate, results spanning a range from 32% ee (R) to 60% ee (S) were obtained (Delta ee = 92%) with 1,5-diaza-cis-decalin ligands differing only in the location of two methyl substituents. Unlike many other diamines that have been employed in asymmetric lithiation-substitution reactions, the limited conformational flexibility of the 1,5-diaza-cis-decalins is analogous to (-)-sparteine such that these results may permit the construction of structure-activity relationships.

Aza Compounds↗
PubMed1990

Changes in red blood cell choline and choline-bound lipids with oral lithium.

The influence of oral lithium on the concentration of red blood cell choline (Ch), lecithin, glycerophosphorylcholine (GPCh) and phosphorylcholine (PCh) was studied. The concentration of RBC Ch was significantly elevated and the concentration of lecithin, GPCh and PCh significantly depressed in 16 patients on oral lithium compared to 9 age-matched controls. We conclude that lithium markedly depletes the red blood cell of choline containing compounds including lecithin. These changes may be responsible for both the therapeutic efficacy and the toxicity of lithium.

Administration, Oral↗
PubMed2002

The effect of veneering and heat treatment on the flexural strength of Empress 2 ceramics.

OBJECTIVES: The aims of the study were to test and compare the biaxial flexural strength and reliability of Empress 2 ceramics after heat treatment and the addition of the veneering material and to characterise their microstructures. METHODS: Forty disc specimens (2 x 14 mm) and forty disc specimens (1 x 14 mm) were produced by heat pressing in the EP 500 press furnace. Group 1 (2 x 14 mm Empress 2 core) was as heat pressed and group 2 (2 x 14 mm Empress 2 core) was subjected to the recommended firing cycles. Groups 3 and 4 (1 x 14 mm Empress 2 core) were veneered with the dentine material and heat-treated as per group 2. Groups 1, 2 and 3 were lapped to 800 grit silicon carbide paper on the compressive surface only and group 4 on both the compressive and tensile test surfaces. Twenty disc specimens per group were tested using the biaxial flexure test at a crosshead speed of 0.15 mm/min. Specimens were characterised using X-ray diffraction (XRD) and secondary electron imaging (SEM). RESULTS: Mean biaxial flexural strengths (MPa+/-SD) were group 1: 265.5+/-25.7; group 2: 251.3+/-30.2; group 3: 258.6+/-21.4 and group 4: 308.6+/-37.7. There was no statistical difference between groups 1, 2 and 3 (p>0.05), but differences for group 4 (p<0.05). XRD and SEM revealed lithium disilicate and lithium orthophosphate in the Empress 2 core material and an amorphous glass and some evidence of a crystalline phase in the dentine material. CONCLUSIONS; Veneering or heat treatment of Empress 2 ceramics did not significantly affect the mean biaxial flexural strength (p>0.05) or reliability. Surface modification of the Empress 2 core material increased the mean biaxial flexural strength (p<0.05).

Carbon Compounds, Inorganic↗
PubMed2001

Use of antipsychotic drugs and lithium in mania.

BACKGROUND: Studies highlighting the difficulties associated with lithium suggest that the role of antipsychotic drugs and mood stabilizers in bipolar disorder should be reconsidered. AIMS: To review the efficacy and mode of action of antipsychotic drugs in mania, and to consider the differences between official guidelines and routine clinical practice in the use of these agents for mania. METHOD: Review of research, guideline- and practice-based literature. RESULTS: Guidelines recommend lithium or valproate as first-line treatments for mania, and antipsychotic agents only as 'adjuncts' for agitation, dangerous behaviour or psychosis. However, in routine practice, antipsychotic drugs are often prescribed. The effectiveness of these agents in mania has been established by several studies; newer atypical compounds demonstrate antimanic efficacy with a reduced incidence of neurological side-effects. CONCLUSION: Antipsychotic drugs are important in the treatment of bipolar disorder and mania. Future studies should evaluate the long-term efficacy and safety of newer atypical antipsychotic agents, and the place of anticonvulsants in combination with antipsychotics in bipolar disorder.

Antimanic Agents↗
PubMed2006

Hydrogen release from mixtures of lithium borohydride and lithium amide: a phase diagram study.

We recently reported the synthesis of a new quaternary hydride in the lithium-boron-nitrogen-hydrogen quaternary phase diagram with the approximate composition LiB0.33N0.67H2.67 having a theoretical hydrogen content of 11.9 wt %. This new compound forms by the reaction of appropriate amounts of lithium amide (LiNH2) and lithium borohydride (LiBH4) and releases greater than 10 wt % hydrogen when heated. A small amount of ammonia, 2-3 mol % of the generated gas, is also released. We now report a study of hydrogen and ammonia release from the series of reactant mixtures (LiNH2)x(LiBH4)1-x, where x=0.667 corresponds to the composition LiB0.33N0.67H2.67. We measured hydrogen and ammonia release amounts as a function of composition and found that maximum hydrogen and minimum ammonia release do occur for x=0.667. We also present evidence for an additional new quaternary phase and for two possibly metastable phases in this system.

Journal Article↗
PubMed1981

Effect of lithium and sodium ions on opiate- and dopamine-receptor binding.

The effects of lithium and sodium were studied in the corpus striatum and cerebral cortex of rats. Lithium was inhibitory at low concentrations but at 20 mM it increased the binding of [G-3H]naloxone (specific activity 15.6 Ci/mmol). Sodium stimulated the high-affinity binding of this compound. Membranes obtained from the rats treated with lithium showed lower specific binding of both [3H]naloxone and [3H]DHM. Binding of [3H]d-alanine Leu-enkephalin was not changed in the brains of lithium-treated rats, but that of [3H]-spiroperidol was lowered. Cerebral cortex and striatum of lithium-treated rats had a decreased apparent dissociation constant and a lower receptor concentration of naloxone binding sites.

Animals↗
PubMed2005

Ionic rotors. preparation, structure, and dynamic solid-state 2D NMR study of the 1,4-diethynylbenzenebis(triphenylborate) dianion.

The reaction between p-(LiC2)2C6H4 (generated in situ from butyllithium and dialkynylbenzene) and 2 equiv of BPh3 affords high yields of [Li(THF)4]2[p-(Ph3BC2)2C6H4], a heretofore missing member of the isoelectronic [p-(Ph3EC2)2C6H4] (E = groups 13-15 element) series. The central phenylene linker is free to rotate in the solid state, as determined by a variable-temperature solid-state 2D spin-echo NMR spectroscopic study. At room temperature, the rate of rotation is at least 20 times faster than that of its carbon-based analogue, presumably a result of Coulombic repulsions minimizing noncovalent interactions between rotating units in the borate salt.

Anions↗