Histamine in Neurotransmission and Brain Diseases

Nuutinen, Saara; Panula, Pertti

doi:10.1007/978-1-4419-8056-4_10

Cited by 117 publications

(90 citation statements)

References 121 publications

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“…While previous research has implicated the histaminergic system in the pathophysiology of schizophrenia, 5,6,41 ABT-288 did not demonstrate pro-cognitive effects in stable subjects with schizophrenia. In our opinion, the lack of effect in this and other studies of other H3 antagonists published in peer reviewed journals or presented at scientific symposia lead us to conclude that this is not a viable target to elicit cognitive improvement in CIAS or other cognition-related indications.…”

Section: Abt-288 and Cognitive Impairment In Schizophreniamentioning

confidence: 77%

A Randomized Trial of the Efficacy and Safety of the H3 Antagonist ABT-288 in Cognitive Impairment Associated With Schizophrenia

Haig

Bain

Robieson

et al. 2014

Schizophrenia Bulletin

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Introduction: ABT-288 is a highly potent histamine-3 receptor antagonist that has demonstrated pro-cognitive effects in preclinical models relevant to schizophrenia. This study evaluated the efficacy and safety of two doses of ABT-288 in the treatment of cognitive impairment associated with schizophrenia. Methods: A randomized, double-blind, placebo-controlled, parallel-group 12-week study was conducted at 23 centers in the United States. Clinically stable subjects with schizophrenia were randomized in an equal ratio to ABT-288 10 mg, ABT-288 25 mg, or placebo once daily while continuing their antipsychotic regimen. The primary efficacy measure was the change from baseline to day 84 evaluation on the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) composite score vs placebo. Secondary measures included cognitive functioning and psychiatric scales. Safety assessments and sparse pharmacokinetic sampling were also conducted. Results: A total of 214 subjects were randomized. The mean baseline MCCB composite score was 28.4. Approximately 80% of subjects completed the study. The MCCB composite score mean change from baseline to day 84 was numerically worse for both the 10 mg (1.90, P = .618) and 25 mg (0.64, P = .946) doses of ABT-288 vs placebo (2.19). Results from the secondary measures were consistent with the primary analysis. Subjects' schizophrenia symptoms remained stable throughout the study as evidenced by stable Positive and Negative Syndrome Scale scores. Overall, study medication was tolerated; however, an increased incidence of psychosis-related and sleep-related adverse events was associated with ABT-288. Discussion: Neither dose of ABT-288 resulted in cognitive improvement in clinically stable adults with schizophrenia.

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Section: Abt-288 and Cognitive Impairment In Schizophreniamentioning

confidence: 77%

A Randomized Trial of the Efficacy and Safety of the H3 Antagonist ABT-288 in Cognitive Impairment Associated With Schizophrenia

Haig

Bain

Robieson

et al. 2014

Schizophrenia Bulletin

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“…Alterations in histaminergic pathways are known to have far-reaching consequences and it is therefore not surprising that histamine neurotransmission has been implicated in a number of neurological conditions [62][63][64][65][66]. For example, in post-mortem studies of patients with Alzheimer disease, levels of histamine were reduced in the hypothalamus, hippocampus and temporal lobes when compared to controls [67].…”

mentioning

confidence: 99%

Histaminergic modulation in Tourette syndrome

Cox

Seri

Cavanna

2016

Expert Opinion on Orphan Drugs

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“…It acts as a neurotransmitter in the central nervous system (1), chemical mediator of allergic reactions (2), and activator of various biological processes including gastric acid secretion (3), capillary dilatation, and smooth muscle contraction (2). Histidine decarboxylase (HDC 3 ; EC 4.1.1.22) catalyzes the rate-limiting reaction in histamine biosynthesis.…”

mentioning

confidence: 99%

Structural Study Reveals That Ser-354 Determines Substrate Specificity on Human Histidine Decarboxylase

Kakemoto

Nitta

Ueno

et al. 2012

Journal of Biological Chemistry

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Background: HDC catalyzes the rate-limiting step in histamine biosynthesis. Results: A mutation based on the crystal structure of HDC changed the substrate selectivity from L-histidine to L-DOPA. Conclusion: The molecular basis for substrate specificity and recognition of group II PLP-dependent decarboxylases were clarified. Significance: Knowledge of the HDC tertiary structure now makes it possible to design novel drugs that prevent histamine biosynthesis.

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Histamine in Neurotransmission and Brain Diseases

Cited by 117 publications

References 121 publications

A Randomized Trial of the Efficacy and Safety of the H3 Antagonist ABT-288 in Cognitive Impairment Associated With Schizophrenia

A Randomized Trial of the Efficacy and Safety of the H3 Antagonist ABT-288 in Cognitive Impairment Associated With Schizophrenia

Histaminergic modulation in Tourette syndrome

Structural Study Reveals That Ser-354 Determines Substrate Specificity on Human Histidine Decarboxylase

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