&lt;p&gt;&lt;em&gt;OPRM1&lt;/em&gt; A118G Polymorphisms and Its Role in Opioid Addiction: Implication on Severity and Treatment Approaches&lt;/p&gt;

Taqi, Malik Mumtaz; Faisal, Muhammad; Zaman, Hadar

doi:10.2147/pgpm.s198654

Cited by 32 publications

(21 citation statements)

References 82 publications

(91 reference statements)

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“…However, prenatal morphine did not alter the locomotor response to morphine in the AG and GG mice ( Robinson et al, 2020 ). Single nucleotide polymorphisms in Oprm1 alter the receptor affinity for endogenous opioid ligands and availability of MOR which, in turn, can affect neurotransmission in key reward pathways ( Peciña et al, 2015 ; Zhang et al, 2015 ; Taqi et al, 2019 ). The most commonly studied SNP in OPRM1 is the A118G SNP in exon 1 which is associated with altered drug, alcohol, and nicotine dependence in humans ( Mague and Blendy, 2010 ).…”

Section: Potential Molecular Mechanisms Underlying Altered Reward Behmentioning

confidence: 99%

Prenatal Opioid Exposure Enhances Responsiveness to Future Drug Reward and Alters Sensitivity to Pain: A Review of Preclinical Models and Contributing Mechanisms

Grecco

Atwood

2020

eNeuro

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The opioid crisis has resulted in an unprecedented number of neonates born with prenatal opioid exposure (POE); however, the long-term effects of POE on offspring behavior and neurodevelopment remain relatively unknown. The advantages and disadvantages of the various preclinical POE models developed over the last several decades are discussed in the context of clinical and translational relevance. Although considerable and important variability exists among preclinical models of POE, the examination of these preclinical models has revealed that opioid exposure during the prenatal period contributes to maladaptive behavioral development as offspring mature including an altered responsiveness to rewarding drugs and increased pain response. The present review summarizes key findings demonstrating the impact of POE on offspring drug selfadministration, drug consumption, the reinforcing properties of drugs, drug tolerance, and other reward-related behaviors such as hypersensitivity to pain. Potential underlying molecular mechanisms which may contribute this enhanced addictive phenotype in POE offspring are further discussed with special attention given to key brain regions associated with reward including the striatum, prefrontal cortex, ventral tegmental area, hippocampus, and amygdala. Improvements in preclinical models and further areas of study are also identified which may advance the translational value of findings and help address the growing problem of POE in clinical populations. Significance Statement As the number of the infants born following prenatal opioid exposure continues to increase, there is a greater need to employ preclinical models to study the potential consequences of POE and brain and behavioral development. A large body of evidence indicates POE is associated with alterations in reward-related behavior and molecular adaptations in reward neurocircuitry. This review seeks to: (1) provide an overview of the various types of preclinical models developed over the last few decades; (2) review the numerous behavioral studies examining drug-reward related behavior in offspring with POE; and (3) discuss potential contributing molecular mechanisms to this enhanced reward phenotype observed in POE offspring.

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Section: Potential Molecular Mechanisms Underlying Altered Reward Behmentioning

confidence: 99%

Prenatal Opioid Exposure Enhances Responsiveness to Future Drug Reward and Alters Sensitivity to Pain: A Review of Preclinical Models and Contributing Mechanisms

Grecco

Atwood

2020

eNeuro

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“…Estudios farmacogenéticos demuestran que el aclaramiento de metadona puede ser regulado por variantes en el citocromo (CYP) CYP2B6 y CYP3A4*22, enzimas metabolizadoras de la metadona (Csajka et al, 2016); esto es una herramienta que ayudaría a dosificar adecuadamente la farmacoterapia de forma personalizada segura, eficaz, optimizada y dirigida, tomando en cuenta los factores etnicos, ambientales y polimorfismos genéticos (Berrettini, 2017;Eissenberg & Aurora, 2019). Otros estudios han demostrado que individuos con polimorfismo de OPRM1 A118G responden bien al tratamiento con naltrexona, estos hallazgos puede determinar que la respuesta a una farmacoterapia del paciente requiere de menor dosis de naltroxona para producir el efecto terapéutico deseado evitando la toxicidad relacionada con altas dosis de tratamiento e incluso la muerte en los peores casos (Taqi et al, 2019).…”

Section: Resultsunclassified

Farmacología y Epidemiología de Opioides

Cardoso‐Ortiz

López-Luna

Lor

et al. 2020

rbio

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Los opioides desde hace muchos años son los analgésicos más utilizados y efectivos para el tratamiento del dolor. Este trabajo da a conocer la clasificación farmacológica, usos terapéuticos, riesgos a la salud y reacciones adversas de los opioides como fármacos, planteando el paradigma del usar este tipo de fármacos para el control del dolor, sin embargo se han convertido en un problema de salud en distintos países ya que en ciertas circunstancias tienen un alto potencial de causar adicción. Además de su uso contra el dolor, los opioides son utilizados como antidiarreicos, antitusivos y para el tratamiento de diversas sintomatologías. A pesar de los efectos adversos, el mal uso y abuso de los opioides; se consideran imprescindibles en la terapia contra el dolor. Actualmente las investigaciones farmacéuticas trabajan en la búsqueda constante de nuevos fármacos con efectos menos severos y con potencia analgésica

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“…The D 40 allele frequency is higher in Asian populations (36%) than in European (19%) and African (2.4%) populations (rs1799971 in gnomAD data base). However, the relevance of N 40 D for opioid treatment and addiction is still under debate (Walter and Lötsch, 2009;Taqi et al, 2019;Ho et al, 2020). Notably, there are also GoF variants in OPRM1.…”

Section: (Supplementalmentioning

confidence: 99%

Mutations in G Protein–Coupled Receptors: Mechanisms, Pathophysiology and Potential Therapeutic Approaches

Schöneberg¹,

Liebscher²

2020

Pharmacol Rev

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There are approximately 800 annotated G protein-coupled receptor (GPCR) genes, making these membrane receptors members of the most abundant gene family in the human genome. Besides being involved in manifold physiologic functions and serving as important pharmacotherapeutic targets, mutations in 55 GPCR genes cause about 66 inherited monogenic diseases in humans. Alterations of nine GPCR genes are causatively involved in inherited digenic diseases. In addition to classic gain-and loss-of-function variants, other aspects, such as biased signaling, trans-signaling, ectopic expression, allele variants of GPCRs, pseudogenes, gene fusion, and gene dosage, contribute to the repertoire of GPCR dysfunctions. However, the spectrum of alterations and GPCR involvement is probably much larger because an additional 91 GPCR genes contain homozygous or hemizygous loss-of-function mutations in human individuals with currently unidentified phenotypes. This review highlights the complexity of genomic alteration of GPCR genes as well as their functional consequences and discusses derived therapeutic approaches. Significance Statement-With the advent of new transgenic and sequencing technologies, the number of monogenic diseases related to G protein-coupled receptor (GPCR) mutants has significantly increased, and our understanding of the functional impact of certain kinds of mutations has substantially improved. Besides the classical gain-and loss-of-function alterations, additional aspects, such as biased signaling, trans-signaling, ectopic expression, allele variants of GPCRs, uniparental disomy, pseudogenes, gene fusion, and gene dosage, need to be elaborated in light of GPCR dysfunctions and possible therapeutic strategies.

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<p><em>OPRM1</em> A118G Polymorphisms and Its Role in Opioid Addiction: Implication on Severity and Treatment Approaches</p>

Cited by 32 publications

References 82 publications

Prenatal Opioid Exposure Enhances Responsiveness to Future Drug Reward and Alters Sensitivity to Pain: A Review of Preclinical Models and Contributing Mechanisms

Prenatal Opioid Exposure Enhances Responsiveness to Future Drug Reward and Alters Sensitivity to Pain: A Review of Preclinical Models and Contributing Mechanisms

Farmacología y Epidemiología de Opioides

Mutations in G Protein–Coupled Receptors: Mechanisms, Pathophysiology and Potential Therapeutic Approaches

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