Allopurinol for the treatment of aggressive behaviour in patients with dementia

Lara, Diogo R.; Cruz, Matheus R S; Xavier, Flávio Merino de Freitas; Souza, Diogo Onofre Gomes de; Moriguchi, Emílio Hideyuki

doi:10.1097/01.yic.0000047783.24295.e5

Cited by 10 publications

(15 citation statements)

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“…Of note, positive effects of allopurinol in refractory epilepsy (Tada et al. , 1991), aggressive behaviour (Lara et al. , 2000; 2003), mania (Machado‐Vieira et al.…”

Section: Introductionmentioning

confidence: 99%

Anti‐nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A₁ adenosine receptors

Schmidt

Böhmer

Antunes

et al. 2008

British J Pharmacology

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Background and purpose:Allopurinol is a potent inhibitor of the enzyme xanthine oxidase, used primarily in the treatment of hyperuricemia and gout. It is well known that purines exert multiple effects on pain transmission. We hypothesized that the inhibition of xanthine oxidase by allopurinol, thereby reducing purine degradation, could be a valid strategy to enhance purinergic activity. The aim of this study was to investigate the anti-nociceptive profile of allopurinol on chemical and thermal pain models in mice. Experimental approach: Mice received an intraperitoneal (i.p.) injection of vehicle (Tween 10%) or allopurinol (10-400 mg kg -1 ). Anti-nociceptive effects were measured with intraplantar capsaicin, intraplantar glutamate, tail-flick or hot-plate tests. Key results: Allopurinol presented dose-dependent anti-nociceptive effects in all models. The opioid antagonist naloxone did not affect these anti-nociceptive effects. The non-selective adenosine-receptor antagonist caffeine and the selective A1 adenosine-receptor antagonist, DPCPX, but not the selective A2A adenosine-receptor antagonist, SCH58261, completely prevented allopurinol-induced anti-nociception. No obvious motor deficits were produced by allopurinol, at doses up to 200 mg kg -1 . Allopurinol also caused an increase in cerebrospinal fluid levels of purines, including the nucleosides adenosine and guanosine, and decreased cerebrospinal fluid concentration of uric acid. Conclusions and implications: Allopurinol-induced anti-nociception may be related to adenosine accumulation. Allopurinol is an old and extensively used compound and seems to be well tolerated with no obvious central nervous system toxic effects at high doses. This drug may be useful to treat pain syndromes in humans.

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“…Of note, positive effects of allopurinol in refractory epilepsy (Tada et al. , 1991), aggressive behaviour (Lara et al. , 2000; 2003), mania (Machado‐Vieira et al.…”

Section: Introductionmentioning

confidence: 99%

Anti‐nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A₁ adenosine receptors

Schmidt

Böhmer

Antunes

et al. 2008

British J Pharmacology

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“…One of the two publications looking at the use of allopurinol in aggression identified a benefit in patients with unspecified dementia. 17 The other examined aggression without a concurrent behavioral disorder association and showed similar benefit. 18 A total of eight individual cases were described between the publications, which identifies the need for more literature to support the use of allopurinol in aggression.…”

Section: Discussionmentioning

confidence: 89%

“…[7][8][9][10][11][12][13][14][15][16] To date, only two publications have evaluated the use of allopurinol specifically in aggression. A case series 17 identified six patients with dementia and aggression who were initiated on allopurinol. The doses ranged from 300-900 mg/day.…”

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confidence: 99%

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Allopurinol for the Treatment of Refractory Aggression: A Case Series

Carr¹,

Straley

Baugh

2017

Pharmacotherapy

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“…Circulating XO is an indicator of hepatic and intestinal damage, and can also acts as a circulating mediator that is accountable for remote organ injury in a variety of pathophysiological conditions. 42 The higher expression of XO also leads to inflammation, [70][71][72] metabolic disorder, 59 diabetes, 73 chronic heart failure, [74][75][76] hypertension, 77,78 cardiovascular diseases, 77,79,80 renal disease, 81 ischemia-reperfusion damage, 70,82 atherosclerosis, 83 dementia, 84 schizophrenia, 85 carcinogenesis, 14,15 endothelial dysfunction, 71,86 tumor lysis syndrome, 87,88 atrial fibrillation, 89 and circulatory shock. XO abets the oxidation/hydroxylation of numerous purines, pterins, aromatic heterocycles, aliphatic and aromatic aldehydes, thereby assist in the detoxification or activation of endogenous compounds and it also plays a vital role in the drug metabolism.…”

Section: Clinical Significancementioning

confidence: 99%

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

Kumar

Joshi

Kler

et al. 2017

Medicinal Research Reviews

101

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Almost all drug molecules become the substrates for oxidoreductase enzymes, get metabolized into more hydrophilic products and eliminated from the body. These metabolites sometime may be more potent, active, inactive, or toxic in nature compared to parent molecule. Xanthine oxidoreductase and aldehyde oxidase belong to molybdenum containing family and are well characterized for their structures and functions, in particular to their ability to oxidize/hydroxylate the xenobiotics. Their upregulated clinical levels causing oxidative stress are associated with pathways either directly involved in the progression of diseases, gout, or indirectly with the succession of other diseases such as diabetes, cancer, etc. Herein, we have put forth a comprehensive review on the xanthine and aldehyde oxidases pertaining to their structures, functions, pathophysiological role, and a comparative analysis of structural insights of xanthine and aldehyde oxidases' binding domains with endogenous ligands or inhibitors. Though both the enzymes are molybdenum containing and are likely to share some common pathways and interact with inhibitors in a similar manner but we have focused on structural prerequisites for inhibitor specificity to both the enzymes keeping in view of the existing X-ray structures. This review also provides futuristic implications in the design of inhibitors derived from inorganic complexes or small organic molecules considering the spatial features and structural insights of both the enzymes.

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Allopurinol for the treatment of aggressive behaviour in patients with dementia

Cited by 10 publications

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Anti‐nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A₁ adenosine receptors

Anti‐nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A₁ adenosine receptors

Allopurinol for the Treatment of Refractory Aggression: A Case Series

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

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Allopurinol for the treatment of aggressive behaviour in patients with dementia

Cited by 10 publications

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Anti‐nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A1 adenosine receptors

Anti‐nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A1 adenosine receptors

Allopurinol for the Treatment of Refractory Aggression: A Case Series

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

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Anti‐nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A₁ adenosine receptors

Anti‐nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A₁ adenosine receptors