Interaction of Diamine Oxidase with Psychostimulant Drugs for ADHD Management

Abstract

Histamine intolerance occurs when there is an imbalance between histamine production and the capacity for histamine degradation. Diamine oxidase (DAO) is the main enzyme for the catabolism of ingested histamine degradation in the gastrointestinal tract and its deficiency has been linked to allergy-like symptoms. Psychostimulant drugs are commonly used to treat Attention Deficit Hyperactivity Disorder (ADHD), but their interaction with DAO is not well characterized. In this work, we evaluated the effects of psychostimulant drugs (methylphenidate and lisdexamfetamine) on in vitro DAO activity and in the human cell line of enterocytes (Caco-2), evaluating DAO expression (mRNA and protein) and DAO activity. Methylphenidate and lisdexamfetamine did not repress the in vitro DAO activity. In addition, in Caco-2 cells, lisdexamfetamine promoted a strong upregulation of DAO mRNA levels, whereas methylphenidate tended to induce DAO activity. To sum up, methylphenidate and lisdexamfetamine treatments do not reduce DAO activity. These findings could be useful for physicians prescribing these two drugs to ADHD patients affected by DAO deficiency.

Prevalence and Clinical Picture of Diamine Oxidase Gene Variants in Children and Adolescents with Attention Deficit Hyperactivity Disorder: A Pilot Study

“…To sum up, our findings are in keeping with the literature linking DAO deficiency with migraine and other medical disorders typically included within the HIT picture. Given that our sample was composed of patients with a primary diagnosis of ADHD, that most of them displayed at least one AOC1 variant related to DAO deficiency, and that some medications approved for the treatment of ADHD (i.e., lisdexamfetamine dimesylate) may improve DAO activity [ 43 ], thus helping to decrease blood histamine levels, we may conclude that some medications for ADHD may help to reduce both ADHD and HIT symptoms by killing two birds with one shot [ 14 ]. Another interesting finding was between variant 2 (rs1049742) and binge eating disorder.…”

Exploring the Relationship between Diamine Oxidase and Psychotropic Medications in Fibromyalgia Treatment, Finding No Reduction in Diamine Oxidase Levels and Activity except with Citalopram

“…The studies conducted by Tobajas and collaborators comprehensively detail the materials and methods employed in this research [50,51] and they are briefly explained below. Details of the assessment of the suppression of diamine oxidase activity by antifibromyalgia medications, evaluation of diamine oxidase activity inhibition by metabolised antifibromyalgia medications, liquid chromatography-tandem mass spectrometry (LC-MS/MS), in vitro cell culturing and experimental treatments, isolation of RNA and quantitative polymerase chain reaction (RT-qPCR) analysis, extraction of proteins, Western blot analysis, and DAO activity within Caco-2 enterocytes are available in the Supplementary Materials.…”

“…Then, after establishing the most effective dose for each drug, Caco-2 cells were placed in 12-well plates for the subsequent assays. The cells were treated with the drugs for 24 h to evaluate the mRNA expression, protein expression, and DAO activity [50,58]. Additionally, aminoguanidine was included in the experimental setup because of its recognised function as an inhibitor of DAO activity [59,60].…”

Diamine Oxidase Interactions with Anti-Inflammatory and Anti-Migraine Medicines in the Treatment of Migraine

“…The materials and methods are essentially explained in the study by Tobajas et al [30], and they are briefly presented below. Details of Assessment of the Suppression of Diamine Oxidase Activity by Anti-Migraine Medications, Evaluation of Diamine Oxidase Activity Inhibition by Metabolized Anti-Migraine Medications, Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), In vitro cell culturing and experimental treatments, Isolation of RNA and quantitative polymerase chain reaction (RT-qPCR) analysis, Extraction of proteins; Western Blot analysis; DAO activity within Caco-2 enterocytes; Statistical methods are available in the Supplementary Materials (Supplementary Material S1, Figure S1).…”