Synthesis and biological evaluation of the major metabolite of atomoxetine: elucidation of a partial κ-opioid agonist effect

Creighton, Christopher J.; Ramabadran, K.; Ciccone, Patrick E.; Liu, Jingchun; Orsini, Michael J.; Reitz, Allen B.

doi:10.1016/j.bmcl.2004.05.018

Cited by 19 publications

(5 citation statements)

References 10 publications

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“…Attention deficit, hyperactivity, and impulsivity, the dominant symptoms of ADHD, can be treated with methylphenidate, dextroamphetamine, and atomoxetine. These stimulants act on different neurotransmitter systems but have in common that they all act also on the EOS (de Wit et al , ; Pietras et al , ; Creighton et al , ; Faraone and Buitelaar, ). Similarly, many other ADHD symptoms can also be explained by an EOS deficiency.…”

Section: Attention‐deficit/hyperactivity Disorder As a Harbinger For mentioning

confidence: 99%

Possible role of a dysregulation of the endogenous opioid system in antisocial personality disorder

Bandelow

Wedekind

2015

Human Psychopharmacology

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Around half the inmates in prison institutions have antisocial personality disorder (ASPD). A recent theory has proposed that a dysfunction of the endogenous opioid system (EOS) underlies the neurobiology of borderline personality disorder (BPD). In the present theoretical paper, based on a comprehensive database and hand search of the relevant literature, this hypothesis is extended to ASPD, which may be the predominant expression of EOS dysfunction in men, while the same pathology underlies BPD in women. According to evidence from human and animal studies, the problematic behaviours of persons with antisocial, callous, or psychopathic traits may be seen as desperate, unconscious attempts to stimulate their deficient EOS, which plays a key role in brain reward circuits. If the needs of this system are not being met, the affected persons experience dysphoric mood, discomfort, or irritability, and strive to increase binding of endogenous opioids to receptors by using the rewarding effects of aggression by exertion of physical or manipulative power on others, by abusing alcohol or substances that have the reward system as target, by creating an "endorphin rush" by self-harm, by increasing the frequency of their sexual contacts, or by impulsive actions and sensation seeking. Symptoms associated with ASPD can be treated with opioid antagonists like naltrexone, naloxone, or nalmefene.

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Section: Attention‐deficit/hyperactivity Disorder As a Harbinger For mentioning

confidence: 99%

Possible role of a dysregulation of the endogenous opioid system in antisocial personality disorder

Bandelow

Wedekind

2015

Human Psychopharmacology

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“…Second-line drugs for ADHD include Atomoxetine, Guanfacine, and Clonidine. 351 , 438 , 460 Atoroxetine is a non-stimulant medication that acts as a selective norepinephrine reuptake inhibitor in ADHD. 440 , 461 Guanfacine is a phenylacetyl guanidine derivative, which is more selective than Clonidine in activating the α2-adrenergic receptor.…”

Section: Therapeutic Developmentmentioning

confidence: 99%

G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders

Wong

et al. 2023

Sig Transduct Target Ther

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Neuropsychiatric disorders are multifactorial disorders with diverse aetiological factors. Identifying treatment targets is challenging because the diseases are resulting from heterogeneous biological, genetic, and environmental factors. Nevertheless, the increasing understanding of G protein-coupled receptor (GPCR) opens a new possibility in drug discovery. Harnessing our knowledge of molecular mechanisms and structural information of GPCRs will be advantageous for developing effective drugs. This review provides an overview of the role of GPCRs in various neurodegenerative and psychiatric diseases. Besides, we highlight the emerging opportunities of novel GPCR targets and address recent progress in GPCR drug development.

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“…Lastly, it should be noted that 4-hydroxyatomoxetine, the human metabolite of atomoxetine, is a partial KOR agonist [65]. Subsequently, it is possible to point to KOR antagonists as potential therapeutic agents for ADHD management, particularly buprenorphine [66].…”

Section: Demographic Clinical and Treatment Outcome Characteristics According To The Presence Of Adhd Symptomatologymentioning

confidence: 99%

Adult-Attention Deficit Hyperactive Disorder Symptoms Seem Not to Influence the Outcome of an Enhanced Agonist Opioid Treatment: A 30-Year Follow-Up

Maremmani

Rocco

Rocca

et al. 2021

IJERPH

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The role of opioids and opioid medications in ADHD symptoms is still largely understudied. We tested the hypothesis that, in Heroin Use Disorder (HUD), when patients are treated with Agonist Opioid medications (AOT), treatment outcome is associated with the presence of Adult Attention-Deficit/Hyperactive Disorder (A-ADHD) symptomatology. A retrospective cohort study of 130 HUD patients in Castelfranco Veneto, Italy, covering 30 years, was divided into two groups according to the Adult ADHD Self-Report Scale (ASRS) score and compared them using demographic, clinical and pharmacological factors. Survival in treatment was studied by utilizing the available data for leaving treatment and relapsing into addictive behavior and for mortality during treatment as poor primary outcomes. Thirty-five HUD subjects (26.9%) were unlikely to have A-ADHD symptomatology, and 95 (73.1%) were likely to have it. Only current age and co-substance use at treatment entry differed significantly between groups. Censored patients were 29 (82.9%) for HUD patients and 70 (73.9%) for A-ADHD/HUD patients (Mantel-Cox test = 0.66 p = 0.415). There were no significant linear trends indicative of a poorer outcome with the presence of A-ADHD after adjustment for demographic, clinical and pharmacological factors. Conclusions: ADHD symptomatology does not seem to exert any influence on the retention in AOT of HUD patients.

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Synthesis and biological evaluation of the major metabolite of atomoxetine: elucidation of a partial κ-opioid agonist effect

Cited by 19 publications

References 10 publications

Possible role of a dysregulation of the endogenous opioid system in antisocial personality disorder

Possible role of a dysregulation of the endogenous opioid system in antisocial personality disorder

G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders

Adult-Attention Deficit Hyperactive Disorder Symptoms Seem Not to Influence the Outcome of an Enhanced Agonist Opioid Treatment: A 30-Year Follow-Up

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