Inhibition of specific adenylyl cyclase isoforms by lithium and carbamazepine, but not valproate, may be related to their antidepressant effect

Mann, Liad; Heldman, Eliahu; Bersudsky, Yuly; Vatner, Stephen F.; Ishikawa, Yoshihiro; Almog, Orna; Belmaker, Robert H.; Agam, Galila

doi:10.1111/j.1399-5618.2009.00762.x

Cited by 37 publications

(21 citation statements)

References 82 publications

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“…It has been reported that CBZ influences the expression of CYP3A4, ABCB1, DRD1, CYP2C8, HLA-B, PLA2G4A, ABCC2, EPHX1, NR1I2, ESR1, CCND1, CYP2B6, GRIK2, NR3C1, and SLC5A5 [15][16][17][18][19][20][21][22] . The genetic variants in ABCC2, EPHX1, TNF, and HSPA1L that affect susceptibility to CBZ can be used to predict maintenance doses of CBZ 21,23-25 .…”

Section: Discussionmentioning

confidence: 99%

Identification of genes induced by carbamazepine in human bronchial epithelial BEAS-2B cells

Song

Kim

Ryu

2011

Toxicol. Environ. Health Sci.

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Some drugs are limited in their clinical application due to their propensity for inducing adverse side effects. We examined some clinical chemotherapeutic agents that have pulmonary toxic effects. Carbamazepine (CBZ) is an antiepileptic agent and its long-term use is associated with interstitial pneumonia, pulmonary fibrosis, and pulmonary infiltration with eosinophilia. CBZ is persistent in the environment and is frequently detected in water systems. A new technique in toxicity screening, "toxicogenomic technology", represents a useful approach for evaluating the toxic properties of new drug candidates early in the drug discovery process and their potential effects on the environment. To this end, we have examined gene expression profiles in BEAS-2B cells (a human bronchial epithelial cell line) following exposure to CBZ, which induced pulmonary toxicity, by using a human oligonucleotide chip. We identified 518 up-and 496 down-regulated genes whose expression had changed by more than 1.5-fold ( p⁄0.01) following CBZ exposure. Gene Ontology (GO) analysis showed elevation in the expression of genes involved in several key biological processes related to pulmonary toxicity, such as cholesterol metabolism, cell proliferation, and cell cycle regulation. In conclusion, the present study indicates that CBZ exerts its toxicity by modulating mRNA expression in BEAS-2B cells. We suggest that genes expressed by CBZ might serve as a molecular signature, which could be used more widely when implemented in combination with more traditional techniques, for the assessment and prediction of toxicity following CBZ-exposure.

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Section: Discussionmentioning

confidence: 99%

Identification of genes induced by carbamazepine in human bronchial epithelial BEAS-2B cells

Song

Kim

Ryu

2011

Toxicol. Environ. Health Sci.

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“…Many putative mechanisms of action of lithium have been proposed . Among them are selective inhibition of specific isoforms of adenylyl cyclase that are associated with antidepressant‐like behaviors in animal models, antagonism at dopamine receptors indirectly through inhibition of GSK 3 enzyme, and increased serotonin (5‐HT) levels in various brain areas such as dorsal hippocampus and lateral hypothalamus with lithium use . Perhaps, the effect of lithium on normalization of the abnormal circadian rhythm in bipolar patients may be of more interest in explaining why it could plausibly be effective in both CH and HH …”

Section: Treatment Optionsmentioning

confidence: 99%

Long‐Term Outcomes and Clinical Characteristics of Hypnic Headache Syndrome: 40 Patients Series From a Tertiary Referral Center

et al. 2016

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HH is an infrequent primary headache disorder that can present with cranial autonomic features. It can persist for years in the elderly. Lithium appeared to be the most effective treatment option, followed by caffeine at bedtime. Caffeine ingestion on awakening with an HH also demonstrated benefit. Cervicogenic headaches in the elderly and presence of active migraine are major confounders in the diagnosis of HHs.

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“…Competition with magnesium for binding sites also modulates actions of lithium on G-protein-mediated cellular signaling transduction pathways (GTP binding and cyclic AMP production) through inhibition of adenylyl cyclase (Ebstein et al, 1976; Ebstein et al, 1978; Andersen and Geisler, 1984; Ebstein et al, 1987; Newman and Belmaker, 1987; Avissar et al, 1988; Mørk and Geisler, 1989; Minadeo et al, 2001; Srinivasan et al, 2004). Lithium selectively inhibits specific isoforms of adenylyl cyclase that are associated with antidepressant-like behaviors in animal models (Mann et al, 2008; Mann et al, 2009). …”

Section: Lithium and Magnesiummentioning

confidence: 99%

Molecular actions and clinical pharmacogenetics of lithium therapy

Can

Schulze

Gould

2014

Pharmacology Biochemistry and Behavior

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Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and in particular mania, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifests beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium’s therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future.

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Inhibition of specific adenylyl cyclase isoforms by lithium and carbamazepine, but not valproate, may be related to their antidepressant effect

Cited by 37 publications

References 82 publications

Identification of genes induced by carbamazepine in human bronchial epithelial BEAS-2B cells

Identification of genes induced by carbamazepine in human bronchial epithelial BEAS-2B cells

Long‐Term Outcomes and Clinical Characteristics of Hypnic Headache Syndrome: 40 Patients Series From a Tertiary Referral Center

Molecular actions and clinical pharmacogenetics of lithium therapy

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