The Alpha-2A Adrenergic Receptor Gene -1291C/G Single Nucleotide Polymorphism is Associated with the Efficacy of Methylphenidate in Treating Taiwanese Children and Adolescents with Attention-Deficit Hyperactivity Disorder

Huang, Hui-Ching; Wu, Lawrence Shih-Hsin; Yu, Shun-Chieh; Wu, Bo-Jian; Lua, Ahai C.; Lee, Shin-Min; Liu, Chao-Zong

doi:10.30773/pi.2017.07.24

Cited by 10 publications

(17 citation statements)

References 39 publications

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“…Although most research on the pharmacological effects of MPH in ADHD is focused on the dopaminergic system, there is a growing body of evidence pointing to the significance of the noradrenergic component as well. Not only has MPH a relatively high affinity for NAT, but it also directly interacts with noradrenergic receptors (Andrews and Lavin 2006 ; Besnard et al 2012 ; Furini et al 2017 ; Gamo et al 2010 ; Huang et al 2018 ). Accordingly, it was reported that MPH binds to several subtypes of α-adrenergic receptors: α 2A (K i = 5.6 µM), α 2B (K i = 2.420 µM), and α 2C (K i = 0.860 µM) (Wenthur 2016 ).…”

Section: Methylphenidate: Chemistry and General Pharmacologymentioning

confidence: 99%

Methylphenidate for attention-deficit/hyperactivity disorder in adults: a narrative review

2021

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Rationale Psychostimulants, including methylphenidate (MPH), are the mainstay of pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD) in adults. Even though MPH is the most commonly used medication for ADHD these days, there are relatively few resources available that provide comprehensive insight into the pharmacological and clinical features of the compound. Objective The aim of this paper is to provide an up-to-date outline of the pharmacology and clinical utility of MPH for ADHD in adult patients. Methods While conducting the narrative review, we applied structured search strategies covering the two major online databases (MEDLINE and Cochrane Central Register of Controlled Trials). In addition, we performed handsearching of reference lists of relevant papers. Results Methylphenidate exhibits multimodal mechanism of action, working primarily as a dopamine and noradrenaline reuptake inhibitor. It also protects the dopaminergic system against the ongoing ‘wearing off’ (by securing a substantial reserve pool of the neurotransmitter, stored in the presynaptic vesicles). In placebo-controlled trials, MPH was shown to be moderately effective both against the core ADHD symptoms (standardized mean difference [SMD], 0.49; 95% confidence interval [CI], 0.35–0.64), and the accompanying emotion regulation deficits (SMD, 0.34; 95% CI, 0.23–0.45). The most common adverse events related to long-term treatment with MPH are decreased appetite (~ 20%), dry mouth (15%), heart palpitations (13%), gastrointestinal infections (~ 10%), and agitation/feeling restless (~ 10%). Conclusions There is substantial body of evidence to suggest that MPH is an effective and safe treatment option for adults with ADHD.

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Section: Methylphenidate: Chemistry and General Pharmacologymentioning

confidence: 99%

Methylphenidate for attention-deficit/hyperactivity disorder in adults: a narrative review

2021

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“…In the literature, the side effect of chorea associated with the use of methylphenidate in therapeutic doses or rapid dose increase for therapeutic purposes has been reported in children 5,6 . This condition is attributed to the prefrontal cortex alpha-2A adrenergic receptor gene polymorphism, which can increase the effectiveness of the drug, or the CES1 gene variation that delays the metabolism of the drug 7,8 . Our patient who had no history of consanguinity have a brother who was receiving 10 mg of methylphenidate daily due to ADHD and he had no side effects such as movement disorder etc..…”

Section: Discussionmentioning

confidence: 99%

Is Every Involuntary Movement Epileptic?

Gurlu

Kendir

Baspinar

et al. 2021

Journal of Emergency Medicine Case Reports

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Introduction: Paroxysmal nonepileptic events are episodic changes in behavior, sensation, or consciousness that are similar to epileptic seizures but not associated with abnormal ictal brain electrophysiological discharges. Here, a case treated as epileptic seizure was presented in order to draw attention to paroxysmal nonepileptic events in differential diagnosis.Case: A 4 years old girl sent to our hospital with the diagnose of status epilepticus due to change in her consciousness, contractions and abnormal movements in her body, arms and legs those started after taking 6 spoonfull syrup of Peditus® (Containing 120 mg paracetamol, 50 mg guaifenesin, 6.25 mg pyrilamine maleate, 5 mg phenylephrine hcl in 5 ml scale) and 5 Medikinet® 10 mg capsules (10 mg methylphenidate hydrochloride in 1 capsule). She was conscious and cooperate and has involuntary snake-like movements throughout her body on admission. The patient's movement disturbances thought as methylphenidate-induced choreoathetosis responded to given haloperidol treatment and any sign of poisoning were not observed in the patient's follow up. Conclusion:Chorea side effects were observed in our patient but not any poisoning symptoms, who received a toxic dose of methylphenidate for her age. This suggests that methylphenidate, a central nervous system stimulant, may have therapeutic, toxic dose limits and side effects profile those associated with individual pharmacogenetic variations. Accurate distinction of chorea from drug-related paroxysmal nonepileptic events will ensure early effective treatment of patients and to protect patients from unnecessary drug risks.

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“…Another study found that the ADRA2A-1291C/G SNP is associated with the efficacy of methylphenidate (MPH) in the treatment of attention deficit/hyperactivity disorder in children and adolescents in Taiwan. Reactive subjects carrying the homozygous-1291G allele are more likely to respond better to MPH therapy, indicating that the -1191C/G SNP is very sensitive to MPH (34). In addition, as seen from the results of the present study, the VAS score of wild-type puerperae was lower than the mutant puerperae at the same time after surgery, while the Ramsay scores of wild-type puerperae 12 h after surgery were significantly higher than the mutant puerperae, indicating that wild-type puerperae are more sensitive to dexmedetomidine than mutant puerperae, probably because genetic mutations alter the structure and/or function of the Figure 7.…”

Section: Discussionmentioning

confidence: 99%

Effect of ADRA2A gene polymorphisms on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women with cesarean section

et al. 2020

Exp Ther Med

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It is well known that differences in drug reactions among individuals are widespread, and therefore the study of genetic polymorphisms of drug targets has become a research hotspot. Dexmedetomidine is clinically effective by acting on α2 adrenergic receptor and the impact of the adrenoceptor α2A gene (ADRA2A) polymorphisms on the anesthetic and analgesic effects of dexmedetomidine is related to the clinical application of dexmedetomidine. The present study aimed to analyze the effects of the rs1800035, rs201376588 and rs775887911 locus single-nucleotide polymorphisms of the ADRA2A on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women. A total of 434 Chinese women undergoing cesarean section were enrolled in this study. A 3-ml fasting venous blood sample was collected from all subjects for genomic DNA extraction and genotype detection. The pre-anesthetic and post-anesthetic pain threshold (PTh), pain tolerance threshold (PTTh), mean arterial pressure, heart rate, blood oxygen saturation, cortisol (Cor) content, blood glucose (Glu) content, opioid usage, patient-controlled analgesia pressing times, surgical satisfaction and postoperative adverse reactions were recorded. The visual analogue scale (VAS) and Ramsay sedation score were evaluated. PTh and PTTh in the wild-type women were higher than those in the women with mutations (P<0.05). The postoperative VAS scores of wild-type women were lower than those of mutants (P<0.05). The Ramsay sedation scores of wild-type patients at 12 h after the operation were significantly higher than in those with mutations (P<0.05). The levels of Cor and Glu in women with mutations were significantly higher than those of wild-type women at 12, 24 and 48 h after surgery (P<0.05). The satisfaction with surgery of wild-type patients was higher than that of patients with mutations (P<0.05). Gene mutations of rs1800035, rs201376588 and rs775887911 loci in the ADRA2A gene reduced the anesthetic and analgesic effect during and after cesarean section in Chinese Han women. Postoperative analgesia of mothers with mutations may require higher doses of analgesics.

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The Alpha-2A Adrenergic Receptor Gene -1291C/G Single Nucleotide Polymorphism is Associated with the Efficacy of Methylphenidate in Treating Taiwanese Children and Adolescents with Attention-Deficit Hyperactivity Disorder

Cited by 10 publications

References 39 publications

Methylphenidate for attention-deficit/hyperactivity disorder in adults: a narrative review

Methylphenidate for attention-deficit/hyperactivity disorder in adults: a narrative review

Is Every Involuntary Movement Epileptic?

Effect of ADRA2A gene polymorphisms on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women with cesarean section

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