«Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens».Proc. Natl. Acad. Sci. U.S.A.106(8): 2915–20.2009.doi:10.1073/pnas.0813179106.PMID19202072.PMC2650365.Bibcode:2009PNAS..106.2915K.https://archive.org/details/sim_proceedings-of-the-national-academy-of-sciences-usa_2009-02-24_106_8/page/2915.«Despite decades of clinical use of methylphenidate for ADHD, concerns have been raised that long-term treatment of children with this medication may result in subsequent drug abuse and addiction. However, meta analysis of available data suggests that treatment of ADHD with stimulant drugs may have a significant protective effect, reducing the risk for addictive substance use (36, 37). Studies with juvenile rats have also indicated that repeated exposure to methylphenidate does not necessarily lead to enhanced drug-seeking behavior in adulthood (38). However, the recent increase of methylphenidate use as a cognitive enhancer by the general public has again raised concerns because of its potential for abuse and addiction (3, 6–10). Thus, although oral administration of clinical doses of methylphenidate is not associated with euphoria or with abuse problems, nontherapeutic use of high doses or i.v. administration may lead to addiction (39, 40).».
«Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens».Proc. Natl. Acad. Sci. U.S.A.106(8): 2915–20.2009.doi:10.1073/pnas.0813179106.PMID19202072.PMC2650365.Bibcode:2009PNAS..106.2915K.https://archive.org/details/sim_proceedings-of-the-national-academy-of-sciences-usa_2009-02-24_106_8/page/2915.«Despite decades of clinical use of methylphenidate for ADHD, concerns have been raised that long-term treatment of children with this medication may result in subsequent drug abuse and addiction. However, meta analysis of available data suggests that treatment of ADHD with stimulant drugs may have a significant protective effect, reducing the risk for addictive substance use (36, 37). Studies with juvenile rats have also indicated that repeated exposure to methylphenidate does not necessarily lead to enhanced drug-seeking behavior in adulthood (38). However, the recent increase of methylphenidate use as a cognitive enhancer by the general public has again raised concerns because of its potential for abuse and addiction (3, 6–10). Thus, although oral administration of clinical doses of methylphenidate is not associated with euphoria or with abuse problems, nontherapeutic use of high doses or i.v. administration may lead to addiction (39, 40).».
«Methylphenidate in children with hyperactivity: review and cost-utility analysis».Pharmacoepidemiol Drug Saf10(2): 85–94.2001.doi:10.1002/pds.564.PMID11499858.
«Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge».CNS Drugs25(7): 539–554.July 2011.doi:10.2165/11589380-000000000-00000.PMID21699268.
«Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults».J. Am. Acad. Child Adolesc. Psychiatry41(2 Suppl): 26S–49S.February 2002.doi:10.1097/00004583-200202001-00003.PMID11833633.
«The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex».Biol. Psychiatry77(11): 940–950.June 2015.doi:10.1016/j.biopsych.2014.09.013.PMID25499957.«The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors.... This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors. Collectively, this evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacologic treatments for attention-deficit/hyperactivity disorder and other conditions associated with PFC dysregulation.».
«Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing».Sports Med.43(5): 301–311.May 2013.doi:10.1007/s40279-013-0030-4.PMID23456493.
Ornoy,Asher(6 February 2018).«Pharmacological Treatment of Attention Deficit Hyperactivity Disorder During Pregnancy and Lactation».Pharmaceutical Research35(3): 46.doi:10.1007/s11095-017-2323-z.PMID29411149.
«Methylphenidate-induced psychosis in adult attention-deficit/hyperactivity disorder: report of 3 new cases and review of the literature».Clinical Neuropharmacology33(4): 204–6.July 2010.doi:10.1097/WNF.0b013e3181e29174.PMID20571380.
«Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management».CNS Drugs27(7): 531–543.June 2013.doi:10.1007/s40263-013-0084-8.PMID23757186.«The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol.... However, fatalities are rare with appropriate care».
«Severe toxicity due to injected but not oral or nasal abuse of methylphenidate tablets».Swiss Med Wkly141: w13267.2011.doi:10.4414/smw.2011.13267.PMID21984207.
«Risks of high-dose stimulants in the treatment of disorders of excessive somnolence: a case-control study».Sleep28(6): 667–72.2005.doi:10.1093/sleep/28.6.667.PMID16477952.
«Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens».Proc. Natl. Acad. Sci. U.S.A.106(8): 2915–20.2009.doi:10.1073/pnas.0813179106.PMID19202072.PMC2650365.Bibcode:2009PNAS..106.2915K.https://archive.org/details/sim_proceedings-of-the-national-academy-of-sciences-usa_2009-02-24_106_8/page/2915.«Despite decades of clinical use of methylphenidate for ADHD, concerns have been raised that long-term treatment of children with this medication may result in subsequent drug abuse and addiction. However, meta analysis of available data suggests that treatment of ADHD with stimulant drugs may have a significant protective effect, reducing the risk for addictive substance use (36, 37). Studies with juvenile rats have also indicated that repeated exposure to methylphenidate does not necessarily lead to enhanced drug-seeking behavior in adulthood (38). However, the recent increase of methylphenidate use as a cognitive enhancer by the general public has again raised concerns because of its potential for abuse and addiction (3, 6–10). Thus, although oral administration of clinical doses of methylphenidate is not associated with euphoria or with abuse problems, nontherapeutic use of high doses or i.v. administration may lead to addiction (39, 40).».
«New treatments for cocaine dependence: a focused review».The International Journal of Neuropsychopharmacology11(3): 425–38.May 2008.doi:10.1017/S1461145707008097.PMID17927843.
«The principles of agonist pharmacotherapy for psychostimulant dependence».Drug and Alcohol Review27(3): 301–8.May 2008.doi:10.1080/09595230801927372.PMID18368612.
«Molecular neurobiology of addiction: what's all the (Δ)FosB about?».The American Journal of Drug and Alcohol Abuse40(6): 428–37.November 2014.doi:10.3109/00952990.2014.933840.PMID25083822.« The strong correlation between chronic drug exposure and ΔFosB provides novel opportunities for targeted therapies in addiction (118), and suggests methods to analyze their efficacy (119). Over the past two decades, research has progressed from identifying ΔFosB induction to investigating its subsequent action (38). It is likely that ΔFosB research will now progress into a new era – the use of ΔFosB as a biomarker.... Conclusions ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a molecular switch (34). As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.».
•«Epigenetic regulation in drug addiction».Annals of Agricultural and Environmental Medicine19(3): 491–6.2012.PMID23020045.«For these reasons, ΔFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre, prefrontal cortex, and other regions of the limbic system. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken... In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. This depends on ΔFosB inhibiting G9a gene expression, i.e. H3K9me2 synthesis which in turn inhibits transcription factors for ΔFosB. For this reason, the observed hyper-expression of G9a, which ensures high levels of the dimethylated form of histone H3, eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks ΔFosB transcription».
•«Transcriptional and epigenetic mechanisms of addiction».Nature Reviews. Neuroscience12(11): 623–37.October 2011.doi:10.1038/nrn3111.PMID21989194.«ΔFosB has been linked directly to several addiction-related behaviors... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states.».
«Manic switch and serotonin syndrome induced by augmentation of paroxetine with methylphenidate in a patient with major depression».Progress in Neuro-Psychopharmacology & Biological Psychiatry34(4): 719–20.May 2010.doi:10.1016/j.pnpbp.2010.03.016.PMID20298736.
«New methylphenidate formulations for the treatment of attention-deficit/hyperactivity disorder».Expert Opinion on Drug Delivery2(1): 121–43.2005.doi:10.1517/17425247.2.1.121.PMID16296740.
«Detection of the novel metabolite ethylphenidate after methylphenidate overdose with alcohol coingestion».Journal of Clinical Psychopharmacology19(4): 362–6.1999.doi:10.1097/00004714-199908000-00013.PMID10440465.
«Methylphenidate and its isomers: their role in the treatment of attention-deficit hyperactivity disorder using a transdermal delivery system».CNS Drugs20(9): 713–38.2006.doi:10.2165/00023210-200620090-00002.PMID16953648.
«Mechanism of action of methylphenidate: insights from PET imaging studies».Journal of Attention Disorders6 Suppl 1: S31-43.1 January 2002.doi:10.1177/070674370200601s05.PMID12685517.
«Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects».Acta Psychiatrica Scandinavica125(2): 114–26.February 2012.doi:10.1111/j.1600-0447.2011.01786.x.PMID22118249.«Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure.».
«Striatal dopamine neurotransmission: regulation of release and uptake».Basal Ganglia6(3): 123–148.August 2016.doi:10.1016/j.baga.2016.02.001.PMID27141430.«Despite the challenges in determining synaptic vesicle pH, the proton gradient across the vesicle membrane is of fundamental importance for its function. Exposure of isolated catecholamine vesicles to protonophores collapses the pH gradient and rapidly redistributes transmitter from inside to outside the vesicle.... Amphetamine and its derivatives like methamphetamine are weak base compounds that are the only widely used class of drugs known to elicit transmitter release by a non-exocytic mechanism. As substrates for both DAT and VMAT, amphetamines can be taken up to the cytosol and then sequestered in vesicles, where they act to collapse the vesicular pH gradient.».
Panizzon L(1944).«La preparazione di piridile piperidil-arilacetonitrili e di alcuni prodotti di trasformazione (Parte Ia)».Helvetica Chimica Acta27: 1748–56.doi:10.1002/hlca.194402701222.
«[Ritalin, a new synthetic compound with specific analeptic components]».Klinische Wochenschrift32(19–20): 445–50.May 1954.doi:10.1007/BF01466968.PMID13164273.
«The Evergreening of Biopharmaceuticals: Time to Defoliate».Journal of Clinical Pharmacology56(4): 383–9.April 2016.doi:10.1002/jcph.642.PMID26388527.
Noven Pharmaceuticals, Inc. (17 Απριλίου 2015). «Daytrana Prescribing Information»(PDF). United States Food and Drug Administration. σελίδες1–33. Αρχειοθετήθηκε από το πρωτότυπο(PDF) στις 23 Ιουνίου 2015. Ανακτήθηκε στις 23 Ιουνίου 2015.
«DAYTRANA»(PDF). United States Food and Drug Administration. Noven Pharmaceuticals, Inc. Οκτωβρίου 2013. Αρχειοθετήθηκε από το πρωτότυπο(PDF) στις 14 Ιουλίου 2014. Ανακτήθηκε στις 13 Ιουνίου 2014.
«FDA»(PDF). Αρχειοθετήθηκε από το πρωτότυπο(PDF) στις 10 Φεβρουαρίου 2017. Ανακτήθηκε στις 30 Ιανουαρίου 2019.
«The Drugs and Cosmetics Rules, 1945». Ministry of Health & Family Welfare. Government of India. 15 Αυγούστου 2013. σελίδες729–730. Αρχειοθετήθηκε από το πρωτότυπο στις 8 Αυγούστου 2016. Ανακτήθηκε στις 5 Δεκεμβρίου 2016.
«Methylphenidate in children with hyperactivity: review and cost-utility analysis».Pharmacoepidemiol Drug Saf10(2): 85–94.2001.doi:10.1002/pds.564.PMID11499858.
«Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge».CNS Drugs25(7): 539–554.July 2011.doi:10.2165/11589380-000000000-00000.PMID21699268.
«Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults».J. Am. Acad. Child Adolesc. Psychiatry41(2 Suppl): 26S–49S.February 2002.doi:10.1097/00004583-200202001-00003.PMID11833633.
«The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex».Biol. Psychiatry77(11): 940–950.June 2015.doi:10.1016/j.biopsych.2014.09.013.PMID25499957.«The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors.... This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors. Collectively, this evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacologic treatments for attention-deficit/hyperactivity disorder and other conditions associated with PFC dysregulation.».
«Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing».Sports Med.43(5): 301–311.May 2013.doi:10.1007/s40279-013-0030-4.PMID23456493.
Ornoy,Asher(6 February 2018).«Pharmacological Treatment of Attention Deficit Hyperactivity Disorder During Pregnancy and Lactation».Pharmaceutical Research35(3): 46.doi:10.1007/s11095-017-2323-z.PMID29411149.
«Methylphenidate-induced psychosis in adult attention-deficit/hyperactivity disorder: report of 3 new cases and review of the literature».Clinical Neuropharmacology33(4): 204–6.July 2010.doi:10.1097/WNF.0b013e3181e29174.PMID20571380.
«Frequency of stimulant treatment and of stimulant-associated mania/hypomania in bipolar disorder patients».Psychopharmacology Bulletin41(4): 37–47.2008.PMID19015628.
«Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management».CNS Drugs27(7): 531–543.June 2013.doi:10.1007/s40263-013-0084-8.PMID23757186.«The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol.... However, fatalities are rare with appropriate care».
«Severe toxicity due to injected but not oral or nasal abuse of methylphenidate tablets».Swiss Med Wkly141: w13267.2011.doi:10.4414/smw.2011.13267.PMID21984207.
«Risks of high-dose stimulants in the treatment of disorders of excessive somnolence: a case-control study».Sleep28(6): 667–72.2005.doi:10.1093/sleep/28.6.667.PMID16477952.
«Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens».Proc. Natl. Acad. Sci. U.S.A.106(8): 2915–20.2009.doi:10.1073/pnas.0813179106.PMID19202072.PMC2650365.Bibcode:2009PNAS..106.2915K.https://archive.org/details/sim_proceedings-of-the-national-academy-of-sciences-usa_2009-02-24_106_8/page/2915.«Despite decades of clinical use of methylphenidate for ADHD, concerns have been raised that long-term treatment of children with this medication may result in subsequent drug abuse and addiction. However, meta analysis of available data suggests that treatment of ADHD with stimulant drugs may have a significant protective effect, reducing the risk for addictive substance use (36, 37). Studies with juvenile rats have also indicated that repeated exposure to methylphenidate does not necessarily lead to enhanced drug-seeking behavior in adulthood (38). However, the recent increase of methylphenidate use as a cognitive enhancer by the general public has again raised concerns because of its potential for abuse and addiction (3, 6–10). Thus, although oral administration of clinical doses of methylphenidate is not associated with euphoria or with abuse problems, nontherapeutic use of high doses or i.v. administration may lead to addiction (39, 40).».
«New treatments for cocaine dependence: a focused review».The International Journal of Neuropsychopharmacology11(3): 425–38.May 2008.doi:10.1017/S1461145707008097.PMID17927843.
«The principles of agonist pharmacotherapy for psychostimulant dependence».Drug and Alcohol Review27(3): 301–8.May 2008.doi:10.1080/09595230801927372.PMID18368612.
«Cellular basis of memory for addiction».Dialogues in Clinical Neuroscience15(4): 431–43.December 2013.PMID24459410.«Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction.... A large body of literature has demonstrated that such ΔFosB induction in D1-type NAc neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41.... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.4».
«Molecular neurobiology of addiction: what's all the (Δ)FosB about?».The American Journal of Drug and Alcohol Abuse40(6): 428–37.November 2014.doi:10.3109/00952990.2014.933840.PMID25083822.« The strong correlation between chronic drug exposure and ΔFosB provides novel opportunities for targeted therapies in addiction (118), and suggests methods to analyze their efficacy (119). Over the past two decades, research has progressed from identifying ΔFosB induction to investigating its subsequent action (38). It is likely that ΔFosB research will now progress into a new era – the use of ΔFosB as a biomarker.... Conclusions ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a molecular switch (34). As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.».
•«Epigenetic regulation in drug addiction».Annals of Agricultural and Environmental Medicine19(3): 491–6.2012.PMID23020045.«For these reasons, ΔFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre, prefrontal cortex, and other regions of the limbic system. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken... In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. This depends on ΔFosB inhibiting G9a gene expression, i.e. H3K9me2 synthesis which in turn inhibits transcription factors for ΔFosB. For this reason, the observed hyper-expression of G9a, which ensures high levels of the dimethylated form of histone H3, eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks ΔFosB transcription».
•«Transcriptional and epigenetic mechanisms of addiction».Nature Reviews. Neuroscience12(11): 623–37.October 2011.doi:10.1038/nrn3111.PMID21989194.«ΔFosB has been linked directly to several addiction-related behaviors... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states.».
«Manic switch and serotonin syndrome induced by augmentation of paroxetine with methylphenidate in a patient with major depression».Progress in Neuro-Psychopharmacology & Biological Psychiatry34(4): 719–20.May 2010.doi:10.1016/j.pnpbp.2010.03.016.PMID20298736.
«New methylphenidate formulations for the treatment of attention-deficit/hyperactivity disorder».Expert Opinion on Drug Delivery2(1): 121–43.2005.doi:10.1517/17425247.2.1.121.PMID16296740.
«Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol».Drug Metabolism and Disposition28(6): 620–4.2000.PMID10820132.
«Detection of the novel metabolite ethylphenidate after methylphenidate overdose with alcohol coingestion».Journal of Clinical Psychopharmacology19(4): 362–6.1999.doi:10.1097/00004714-199908000-00013.PMID10440465.
«Methylphenidate and its isomers: their role in the treatment of attention-deficit hyperactivity disorder using a transdermal delivery system».CNS Drugs20(9): 713–38.2006.doi:10.2165/00023210-200620090-00002.PMID16953648.
«Mechanism of action of methylphenidate: insights from PET imaging studies».Journal of Attention Disorders6 Suppl 1: S31-43.1 January 2002.doi:10.1177/070674370200601s05.PMID12685517.
«Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects».Acta Psychiatrica Scandinavica125(2): 114–26.February 2012.doi:10.1111/j.1600-0447.2011.01786.x.PMID22118249.«Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure.».
«Striatal dopamine neurotransmission: regulation of release and uptake».Basal Ganglia6(3): 123–148.August 2016.doi:10.1016/j.baga.2016.02.001.PMID27141430.«Despite the challenges in determining synaptic vesicle pH, the proton gradient across the vesicle membrane is of fundamental importance for its function. Exposure of isolated catecholamine vesicles to protonophores collapses the pH gradient and rapidly redistributes transmitter from inside to outside the vesicle.... Amphetamine and its derivatives like methamphetamine are weak base compounds that are the only widely used class of drugs known to elicit transmitter release by a non-exocytic mechanism. As substrates for both DAT and VMAT, amphetamines can be taken up to the cytosol and then sequestered in vesicles, where they act to collapse the vesicular pH gradient.».
«[Ritalin, a new synthetic compound with specific analeptic components]».Klinische Wochenschrift32(19–20): 445–50.May 1954.doi:10.1007/BF01466968.PMID13164273.
«The Evergreening of Biopharmaceuticals: Time to Defoliate».Journal of Clinical Pharmacology56(4): 383–9.April 2016.doi:10.1002/jcph.642.PMID26388527.
«The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex».Biol. Psychiatry77(11): 940–950.June 2015.doi:10.1016/j.biopsych.2014.09.013.PMID25499957.«The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors.... This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors. Collectively, this evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacologic treatments for attention-deficit/hyperactivity disorder and other conditions associated with PFC dysregulation.».
«Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens».Proc. Natl. Acad. Sci. U.S.A.106(8): 2915–20.2009.doi:10.1073/pnas.0813179106.PMID19202072.PMC2650365.Bibcode:2009PNAS..106.2915K.https://archive.org/details/sim_proceedings-of-the-national-academy-of-sciences-usa_2009-02-24_106_8/page/2915.«Despite decades of clinical use of methylphenidate for ADHD, concerns have been raised that long-term treatment of children with this medication may result in subsequent drug abuse and addiction. However, meta analysis of available data suggests that treatment of ADHD with stimulant drugs may have a significant protective effect, reducing the risk for addictive substance use (36, 37). Studies with juvenile rats have also indicated that repeated exposure to methylphenidate does not necessarily lead to enhanced drug-seeking behavior in adulthood (38). However, the recent increase of methylphenidate use as a cognitive enhancer by the general public has again raised concerns because of its potential for abuse and addiction (3, 6–10). Thus, although oral administration of clinical doses of methylphenidate is not associated with euphoria or with abuse problems, nontherapeutic use of high doses or i.v. administration may lead to addiction (39, 40).».
«Cellular basis of memory for addiction».Dialogues in Clinical Neuroscience15(4): 431–43.December 2013.PMID24459410.«Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction.... A large body of literature has demonstrated that such ΔFosB induction in D1-type NAc neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41.... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.4».
«Molecular neurobiology of addiction: what's all the (Δ)FosB about?».The American Journal of Drug and Alcohol Abuse40(6): 428–37.November 2014.doi:10.3109/00952990.2014.933840.PMID25083822.« The strong correlation between chronic drug exposure and ΔFosB provides novel opportunities for targeted therapies in addiction (118), and suggests methods to analyze their efficacy (119). Over the past two decades, research has progressed from identifying ΔFosB induction to investigating its subsequent action (38). It is likely that ΔFosB research will now progress into a new era – the use of ΔFosB as a biomarker.... Conclusions ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a molecular switch (34). As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.».
•«Epigenetic regulation in drug addiction».Annals of Agricultural and Environmental Medicine19(3): 491–6.2012.PMID23020045.«For these reasons, ΔFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre, prefrontal cortex, and other regions of the limbic system. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken... In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. This depends on ΔFosB inhibiting G9a gene expression, i.e. H3K9me2 synthesis which in turn inhibits transcription factors for ΔFosB. For this reason, the observed hyper-expression of G9a, which ensures high levels of the dimethylated form of histone H3, eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks ΔFosB transcription».
•«Transcriptional and epigenetic mechanisms of addiction».Nature Reviews. Neuroscience12(11): 623–37.October 2011.doi:10.1038/nrn3111.PMID21989194.«ΔFosB has been linked directly to several addiction-related behaviors... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states.».
«Striatal dopamine neurotransmission: regulation of release and uptake».Basal Ganglia6(3): 123–148.August 2016.doi:10.1016/j.baga.2016.02.001.PMID27141430.«Despite the challenges in determining synaptic vesicle pH, the proton gradient across the vesicle membrane is of fundamental importance for its function. Exposure of isolated catecholamine vesicles to protonophores collapses the pH gradient and rapidly redistributes transmitter from inside to outside the vesicle.... Amphetamine and its derivatives like methamphetamine are weak base compounds that are the only widely used class of drugs known to elicit transmitter release by a non-exocytic mechanism. As substrates for both DAT and VMAT, amphetamines can be taken up to the cytosol and then sequestered in vesicles, where they act to collapse the vesicular pH gradient.».
Noven Pharmaceuticals, Inc. (17 Απριλίου 2015). «Daytrana Prescribing Information»(PDF). United States Food and Drug Administration. σελίδες1–33. Αρχειοθετήθηκε από το πρωτότυπο(PDF) στις 23 Ιουνίου 2015. Ανακτήθηκε στις 23 Ιουνίου 2015.
«DAYTRANA»(PDF). United States Food and Drug Administration. Noven Pharmaceuticals, Inc. Οκτωβρίου 2013. Αρχειοθετήθηκε από το πρωτότυπο(PDF) στις 14 Ιουλίου 2014. Ανακτήθηκε στις 13 Ιουνίου 2014.
«The Drugs and Cosmetics Rules, 1945». Ministry of Health & Family Welfare. Government of India. 15 Αυγούστου 2013. σελίδες729–730. Αρχειοθετήθηκε από το πρωτότυπο στις 8 Αυγούστου 2016. Ανακτήθηκε στις 5 Δεκεμβρίου 2016.
