Role of Donepezil in Autism: Its Conduciveness in Psychopharmacotherapy

Srivastava, Rohit Kant; Agarwal, Medhavi; Pundhir, Ashish

doi:10.1155/2011/563204

Cited by 11 publications

(9 citation statements)

References 10 publications

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“…donepezil and galantamine), which, in general, increase cholinergic tone at the synapse [129], cause a pronounced improvement in typical symptoms associated with autism (e.g. verbal communication, eye to eye contact, and emotional responsiveness) in a single case report [130]. Similarly in a randomized, double-blind, placebo-controlled clinical trial, galantamine was shown to be safe and relatively effective in alleviating some autism-related symptoms (e.g.…”

Section: Neurodevelopmental Disordersmentioning

confidence: 99%

Nicotinic ACh receptors as therapeutic targets in CNS disorders

Dineley

Pandya

Yakel

2015

Trends in Pharmacological Sciences

404

345

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The neurotransmitter acetylcholine (ACh) can regulate neuronal excitability by acting on the cys-loop cation-conducting ligand-gated nicotinic ACh receptor channels (nAChRs). These receptors are widely distributed throughout the central nervous system, being expressed on neurons and non-neuronal cells, where they participate in a variety of physiological responses such as anxiety, the central processing of pain, food intake, nicotine seeking behavior, and cognitive functions. In the mammalian brain, nine different subunits have been found thus far, which assemble into pentameric complexes with much subunit diversity; however the α7 and α4β2 subtypes predominate in the CNS. Neuronal nAChR dysfunction is involved in the pathophysiology of many neurological disorders. Here we will briefly discuss the functional makeup and expression of the nAChRs in the mammalian brain, and their role as targets in neurodegenerative diseases (in particular Alzheimer’s disease), neurodevelopmental disorders (in particular autism and schizophrenia), and neuropathic pain.

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Section: Neurodevelopmental Disordersmentioning

confidence: 99%

Nicotinic ACh receptors as therapeutic targets in CNS disorders

Dineley

Pandya

Yakel

2015

Trends in Pharmacological Sciences

404

345

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“…Thus, it was suggested that the loss of nAChR functionality in the brain could be responsible for the ASD phenotype (Martin‐Ruiz et al., 2004). Administration of acetylcholine receptor activator donepezil to an ASD‐affected boy proved beneficial for his cognitive skills after 6 weeks of treatment (Srivastava, Agarwal, & Pundhir, 2011). A randomized double‐blind placebo‐controlled trial using glutamine in autistic children showed significant improvements for some ASD clinical signs (Ghaleiha et al., 2014).…”

Section: Reviewmentioning

confidence: 99%

Autism throughout genetics: Perusal of the implication of ion channels

et al. 2018

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BackgroundAutism spectrum disorder (ASD) comprises a group of neurodevelopmental psychiatric disorders characterized by deficits in social interactions, interpersonal communication, repetitive and stereotyped behaviors and may be associated with intellectual disabilities. The description of ASD as a synaptopathology highlights the importance of the synapse and the implication of ion channels in the etiology of these disorders.MethodsA narrative and critical review of the relevant papers from 1982 to 2017 known by the authors was conducted.ResultsGenome‐wide linkages, association studies, and genetic analyses of patients with ASD have led to the identification of several candidate genes and mutations linked to ASD. Many of the candidate genes encode for proteins involved in neuronal development and regulation of synaptic function including ion channels and actors implicated in synapse formation. The involvement of ion channels in ASD is of great interest as they represent attractive therapeutic targets. In agreement with this view, recent findings have shown that drugs modulating ion channel function are effective for the treatment of certain types of patients with ASD.ConclusionThis review describes the genetic aspects of ASD with a focus on genes encoding ion channels and highlights the therapeutic implications of ion channels in the treatment of ASD.

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“…Most studies focused on the impact on Alzheimer's disease, yet a handful of studies examined the effect of the CNS-specific AChEI Donepezil on ASD symptoms. In two open-label (Buckley et al, 2011;Hardan and Handen, 2002) and one case-study (Srivastava et al, 2011), the drug was found useful in reducing overall ASD severity. Two double-blind placebo-controlled studies were conducted (Chez et al, 2003;Handen et al, 2011), showing amelioration in ASD symptoms after treatment with the drug.…”

Section: Introductionmentioning

confidence: 97%

Acetylcholine Elevation Relieves Cognitive Rigidity and Social Deficiency in a Mouse Model of Autism

Karvat

Kimchi

2013

Neuropsychopharmacol

164

136

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Autism spectrum disorders (ASD) are defined by behavioral deficits in social interaction and communication, repetitive stereotyped behaviors, and restricted interests/cognitive rigidity. Recent studies in humans and animal-models suggest that dysfunction of the cholinergic system may underlie autism-related behavioral symptoms. Here we tested the hypothesis that augmentation of acetylcholine (ACh) in the synaptic cleft by inhibiting acetylcholinesterase may ameliorate autistic phenotypes. We first administered the acetylcholinesterase inhibitor (AChEI) Donepezil systemically by intraperitoneal (i.p.) injections. Second, the drug was injected directly into the rodent homolog of the caudate nucleus, the dorsomedial striatum (DMS), of the inbred mouse strain BTBR T þ tf/J (BTBR), a commonly-used model presenting all core autism-related phenotypes and expressing low brain ACh levels. We found that i.p. injection of AChEI to BTBR mice significantly relieved autism-relevant phenotypes, including decreasing cognitive rigidity, improving social preference, and enhancing social interaction, in a dose-dependent manner. Microinjection of the drug directly into the DMS, but not into the ventromedial striatum, led to significant amelioration of the cognitive-rigidity and social-deficiency phenotypes. Taken together, these findings provide evidence of the key role of the cholinergic system and the DMS in the etiology of ASD, and suggest that elevated cognitive flexibility may result in enhanced social attention. The potential therapeutic effect of AChEIs in ASD patients is discussed.

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Role of Donepezil in Autism: Its Conduciveness in Psychopharmacotherapy

Cited by 11 publications

References 10 publications

Nicotinic ACh receptors as therapeutic targets in CNS disorders

Nicotinic ACh receptors as therapeutic targets in CNS disorders

Autism throughout genetics: Perusal of the implication of ion channels

Acetylcholine Elevation Relieves Cognitive Rigidity and Social Deficiency in a Mouse Model of Autism

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