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Bipolar disorder (BD) poses a significant public health concern, with roughly one‐quarter of sufferers attempting suicide. BD is characterized by manic and depressive mood cycles, the recurrence of which can be effectively curtailed through lithium therapy. Unfortunately, the most frequently employed lithium salt, lithium carbonate (Li2CO3), is associated with a host of adverse health outcomes following chronic use: these unwanted effects range from relatively minor inconveniences (e.g., polydipsia and polyuria) to potentially major complications (e.g., hypothyroidism and/or renal impairment). As these undesirable effects can limit patient compliance, an alternative lithium compound with a lesser toxicity profile would dramatically improve treatment efficacy and outcomes. Lithium orotate (LiC5H3N2O4; henceforth referred to as LiOr), a compound largely abandoned since the late 1970s, may represent such an alternative. LiOr is proposed to cross the blood–brain barrier and enter cells more readily than Li2CO3, which will theoretically allow for reduced dosage requirements and ameliorated toxicity concerns. This review addresses the controversial history of LiOr, complete with discussions of experimental and clinical efficacy, putative mechanisms of action, adverse effects, and its potential future in therapy., Li2CO3 is an efficacious therapeutic option in BD, but a troublesome side effect profile limits patient compliance. LiOr may represent an alternative form of lithium that can enter the brain more readily than Li2CO3, which would theoretically allow for maintenance of efficacy at reduced dosages, thereby mitigating non‐compliance concerns by minimizing the incidence of dose‐dependent side effects.

Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events. Nonetheless, there have been some concerns in the scientific literature regarding orotic acid, and pharmaceutical lithium salts are known to have a narrow therapeutic window, albeit, at lithium equivalent therapeutic doses 5.5–67 times greater than typically recommended for supplemental lithium orotate. To our knowledge, the potential toxicity of lithium orotate has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test in order to further explore its safety. Lithium orotate was not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 28-day, repeated-dose oral toxicity study, rats were administered 0, 100, 200, or 400 mg/kg body weight/day of lithium orotate by gavage. No toxicity or target organs were identified; therefore, a no observed adverse effect level was determined as 400 mg/kg body weight/day. These results are supportive of the lack of a postmarket safety signal from several decades of human consumption.

The current rapid spread of the novel coronavirus (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) calls for a rapid response from the research community. Lithium is widely used to treat bipolar disorder, but has been shown to exhibit antiviral activity. This brief review took a systematic approach to identify six in vitro studies reporting on the influence of lithium on coronaviral infections. We propose mechanistic investigation of the influence of lithium – alone and with chloroquine – on the SARS-CoV-2 infection.

The current rapid spread of the novel coronavirus (2019-nCoV) originating from Wuhan, China, calls for a rapid response from the research community. Lithium is widely used to treat bipolar disorder, but has been shown to exhibit antiviral activity. This brief review took a systematic approach to identify five in vitro studies reporting on the influence of lithium on coronaviral infections. We propose that in the case of urgent need, lithium be explored as a potential treatment or prophylaxis for the novel Wuhan coronavirus (2019-nCoV).

The X-ray crystal structure of the title compound, lithium 1,2,3,6-tetra­hydro-2,6-dioxo-4-pyrimidine­carboxyl­ate monohydrate, Li+·C5H3N2O4−·H2O, was redetermined at a temperature of 110 (2) K. It was now possible to locate all H atoms in the difference Fourier map. The hydrogen-bonding pattern can now be completely described, as well as the coordination mode of the water mol­ecule to the lithium center.

Neutralization of orotic acid (OrH2) by lithium or magnesium hydroxide in aqueous medium yields the crystalline metal orotate hydrates Li(OrH). H2O (1) and Mg(OrH)2. (H2O)6 (2). By single-crystal X-ray diffraction studies it has been shown that 1 (space group P1) forms a layer structure, with lithium in a tetrahedral environment of oxygen atoms from three different orotate( - I) anions (one carboxylate and two uracil oxygen atoms) and the water molecule. 2 (space group P21/c) has been shown to feature a hexaquo complex of magnesium, the Mg(H2O)26 cations being associated with two hydrated OrH⊖ ions only through hydrogen bonds. The anions are also engaged in “base-pairing” hydrogen bonds between the planar uracil ring systems of different units. The results are relevant for applications of magnesium orotates in magnesium therapy.

Neutralization of orotic acid (OrH2) by lithium or magnesium hydroxide in aqueous medium yields the crystalline metal orotate hydrates Li(OrH). H2O (1) and Mg(OrH)2. (H2O)6 (2). By single-crystal X-ray diffraction studies it has been shown that 1 (space group P1) forms a layer structure, with lithium in a tetrahedral environment of oxygen atoms from three different orotate( - I) anions (one carboxylate and two uracil oxygen atoms) and the water molecule. 2 (space group P21/c) has been shown to feature a hexaquo complex of magnesium, the Mg(H2O)26 cations being associated with two hydrated OrH⊖ ions only through hydrogen bonds. The anions are also engaged in “base-pairing” hydrogen bonds between the planar uracil ring systems of different units. The results are relevant for applications of magnesium orotates in magnesium therapy.

1 The pharmacokinetics of the lithium ion administered as lithium orotate were studied in rats. Parallel studies were carried out with lithium carbonate and lithium chloride. 2 No differences in the uptake, distribution and excretion of the lithium ion were observed between lithium orotate, lithium carbonate and lithium chloride after single intraperitoneal, subcutaneous or intragastric injections (0.5-1.0 mEq lithium/kg) or after administration of the lithium salts for 20 days in the food. 3 The findings oppose the notion that the pharmacokinetics of the lithium ion given as lithium orotate differ from lithium chloride or lithium carbonate. 4 Polyuria and polydipsia developed more slowly in rats given lithium orotate than in those given lithium carbonate or lithium chloride, perhaps due to an effect of the orotate anion.

The subjects were 42 alcoholic patients (33 males and 9 females) who were treated with lithium orotate during an alcohol rehabilitation program in a private clinical setting for at least six months. They derive from a total number of 105 patients who received this treatment initially, while the remainder discontinued the treatment within six months. The data were collected from a private practice record and the follow-up varied between six months and 10 years. The 42 patients studied displayed a multitude of complaints in addition to chronic alcoholism. These included liver dysfunction, seizure disorders, headaches, hyperthyroidism, affective disorders. Meniere's syndrome, liver and lung cancers. Thirty-six of the 42 patients studied had been hospitalized at least once for the management of their alcoholism. Lithium orotate was given, 150 mg daily, with a diet low in simple carbohydrates and containing moderate amounts of protein and fat. In addition, calcium orotate (for hepatic involvement), magnesium orotate, bromelaine, and essential phospholipids (for cardiac problems), and supportive measures were instituted, if required. Lithium orotate proved useful as the main pharmacologic agent for the treatment of alcoholism. Ten of the patients had no relapse for over three and up to 10 years, 13 patients remained without relapse for 1 to 3 years, and the remaining 12 had relapses between 6 to 12 months. Lithium orotate therapy was safe and the adverse side effects noted were minor, i.e., eight patients developed muscle weakness, loss of appetite or mild apathy. For these patients, the symptoms subsided when the daily dose was given 4 to 5 times weekly.(ABSTRACT TRUNCATED AT 250 WORDS)

Eight hours after intraperitoneal injections of 1·0, 2·0, and 4·0 m equiv Li kg−1, the serum and brain lithium concentrations of rats were significantly greater after lithium orotate than after lithium carbonate. While little serum lithium remained at 24 h after injection of 2·0 m equiv kg−1 lithium carbonate, two-thirds of the 2 h serum lithium concentration was present 24 h after lithium orotate. Furthermore, the 24 h brain concentration of lithium after lithium orotate was approximately three times greater than that after lithium carbonate. These data suggest the possibility that lower doses of lithium orotate than lithium carbonate may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations.

A recent study by Kling et al (1978) noted the finding of higher lithium concentrations in serum and brain of rats after an intraperitoneal injection (2 mmol lithium kg−1) of lithium orotate as a slurry than of lithium carbonate in solution. The authors suggested that lithium orotate might offer advantages in the treatment of patients. We repeated the experiments of Kling et al but in addition examined the kidney function of the rats. Glomerular filtration rate and urine flow were markedly lower in rats given lithium orotate than in rats given lithium carbonate, sodium chloride or a sham injection. The renal lithium clearance was significantly lower, the kidney weight and the lithium concentrations in serum, kidney and heart significantly higher after injection of lithium orotate than after injection of lithium carbonate. The higher lithium concentrations could be accounted for by the lower kidney function. It seems inadvisable to use lithium orotate for the treatment of patients.