Withdrawal Symptoms Nicotine Dependence
4.6 Concluding Remarks
• Nicotineisoneofthemostpotenttoxicalkaloidswithadependence-inducingeffect, comparable to that of cocaine and heroin. Continued administration in the form of tobaccosmokingespeciallyofcigarettesmayleadtodependence. • NicotineunfoldsitseffectsbyreleasingCNSmessengersubstances,amongwhichdop- amine,NAand5-HTareparticularlyimportant. • NicotineactsbystimulatingnicotinicacetylcholinereceptorsnAChRs:theseareion transportersthatoccurintheperipheralandCNSandarelinkedwithvarioustransmit- tersystems.ThestructureofnAChRshasbeenlargelyelucidatedandthevarioussub- unitsa4b2,a3b4,a7etc.canbeassignedtodifferentneuralstructures.Thesitesof actionofagonistsandcompetitiveandnon-competitiveantagonistscanbelocatedin thereceptorsystem. • Unliketheabsorptionofnicotinefromcigarettes,thenicotineavailablefrompharma- ceuticalformulationsisreleasedverymuchmoreslowlyandinsmallerdoses,andthis isultimatelythereasonfortheproducts’lackofanydependence-inducingeffect. • Inadditiontoexternalinluences,thedevelopmentofnicotinedependencecanalsobe relatedtogeneticfactors.Inthiscontext,thecytochromeP450subenzyme2A6,the distributionofdopaminereceptorsDRD1vs.DRD2andtheirallelesA1vs.A2,as wellastheDATgeneSLC6A3inluencesmokinginitiationandnicotinedependence. • ThenAChRmacromoleculeisaffectedbyseveralpathologicalconditionscongenital myasthenic syndromes, Alzheimer’s and Parkinson’s disease, schizophrenia, some formsofepilepsies,GillesdelaTourettesyndrome.Avarietyofstrategiese.g.,syn- thesisofnAChRagonistsandantagonists,subtlealterationstonAChRfunctionorpar- tialocclusionofthenAChRchannelbyblockingdrugswillresultinnewtherapeutic modalitiesinthenearfuture. References 1.LangleyJN,AndersonHK1892Theactionsofnicotineontheciliaryganglionofthethird cranialnerve.JPhysiolLond13:460–468 2.DaleHH1914Theactionofcertainestersandethersofcholineandtheirrelationtomusca- rine.JPharmacolExpTher6:147–190 3.Karlin A 1993 Structure of nicotinic acetylcholine receptors. Curr Opin Neurobiol 33: 299–309 4.McGeheeDS,RoleLW1995Physiologicaldiversityofnicotinicacetylcholinereceptors expressedbyvertebrateneurons.AnnuRevPhysiol57:521–546 5.BarrantesFJed1998Molecularpathologyofthenicotinicacetylcholinereceptor.In:The nicotineacetylcholinereceptor.Currentviewsandfuturetrends.Springer,Berlin,pp175–216 6.Wonnacott S 1990 Characterization of brain nicotinic receptor sites. In: Wonnacott S, MAHRusselledNicotinepsychopharmacology:molecular,cellularandbehaviouralaspects. OxfordUniversityPress,Oxford,London,pp226–277 7.FloresCM,RogersSW,PabrezaLA,WolfeBB,KellarKJ1992Asubtypeofnicotiniccho- linergicreceptorinratbrainiscomposedofalpha4andbeta2subunitsandisup-regulatedby chronicnicotinetreatment.MolPharmacol41:31–37 8.WilliamsN,SullivanJP,ArnericSP1994Neuronalnicotinicacetylcholinereceptors.DNP 7:205–223 9.SharplesCGV,WonnacottS2001Neuronalnicotinicreceptors.Tocrisreviewsno.19.Tocris Cookson,Avonmouth 10.WonnacottS1990Theparadoxofnicotinicacetylcholinereceptorupregulationbynicotine. TrendsPharmacolSci116:216–219 11.ChenD,PatrickJW1997Thealpha-bungarotoxin-bindingnicotinicacetylcholinereceptor fromratbraincontainsonlythealpha7subunit.JBiolChem272:24024–24029 12.PrinceRJ,SineSM1998Theligandbindingdomainsofthenicotinicacetylcholinereceptor. In:BarrantesFJedThenicotinicacetylcholinereceptor:Currentviewsandfuturetrends. Springer,Berlin,pp31–59 13.GrutterT,ChangeuxJP2001Nicotinicreceptorsinwonderland.TrendsBiochemSci268: 459–463 14.TapperAR,McKinneySL,NashmiR,SchwarzJ,DeshpandeP,LabarcaC,etal2004Nicotine activation of alpha4 receptors: suficient for reward, tolerance, and sensitization. Science 3065698:1029–1032 15.CorringerPJ,LeNovereN,ChangeuxJP2000Nicotinicreceptorsattheaminoacidlevel. AnnuRevPharmacolToxicol40:431–458 16.LenaC,ChangeuxJP1993Allostericmodulationsofthenicotinicacetylcholinereceptor. TrendsNeurosci165:181–186 17.ChangeuxJP,EdelsteinSJ1998Allostericreceptorsafter30years.Neuron21:959–980 18.McGeheeDS,RoleLW1995Physiologicaldiversityofnicotinicacetylcholinereceptors expressedbyvertebrateneurons.AnnuRevPhysiol57:521–546 19.KuryatovA,OlaleFA,ChoiC,LindstromJ2000Acetylcholinereceptorextracellulardomain determinessensitivitytonicotine-inducedinactivation.EurJPharmacol3931–3:11–21 20.McGeheeDS,HeathMJ,GelberS,DevayP,RoleLW1995Nicotineenhancementoffastexcit- atorysynaptictransmissioninCNSbypresynapticreceptors.Science2695231:1692–1696 21.BenwellME,BalfourDJ,AndersonJM1988Evidencethattobaccosmokingincreasesthe densityof–-[3H]nicotinebindingsitesinhumanbrain.JNeurochem504:1243–1247 22.CollinsAC,LuoY,SelvaagS,MarksMJ1994Sensitivitytonicotineandbrainnicotinic receptorsarealteredbychronicnicotineandmecamylamineinfusion.JPharmacolExpTher 2711:125–133 23.GottiC,MorettiM,MaggiR,LonghiR,HankeW,KlinkeN,etal1997Alpha7andalpha8 nicotinicreceptorsubtypesimmunopuriiedfromchickretinahavedifferentimmunological, pharmacologicalandfunctionalproperties.EurJNeurosci9:1201–1211 24.AndersonDJ,ArnericSP1994Nicotinicreceptorbindingof[3H]cytisine,[3H]nicotineand [3H]methylcarbamylcholineinratbrain.EurJPharmacol253:261–267 25.Chavez-Noriega LE, Crona JH, Washburn MS, Urrutia A, Elliott KJ, Johnson EC 1997 Pharmacological characterization of recombinant human neuronal nicotinic acetylcholineParts
» Tobacco Plants and Their Origin Use of Tobacco for Religious Purposes
» The Appropriation of Tobacco by Europeans
» Development of the Cigarette
» Objections to Smoking on Health Grounds
» Women Won Over by the Cigarette
» The Medical Use of Tobacco in the Nineteenth Century
» Tobacco Research in the Twentieth Century
» Tobacco Consumption in the Twentieth Century
» Cigarette Smoking in the USA Since 1965
» Cigarette-Related Mortality in Different Countries
» Smokers and Other Risk Factors
» Smoking Behaviour and Educational Level in the EU
» Non-Disclosure of Findings by the Tobacco Industry
» The Cigarette as a Vehicle for Nicotine Release
» Modifications of Nicotine Release
» Maintaining Nicotine Dependence Nicotine and Dependence
» Marketing of Cigarettes with a “Reduced” Health Risk
» Compensatory Behaviour by Smokers
» Optimising Nicotine Release Nicotine and Dependence
» Importance of Absorption Rate
» Ammonium and pH Manipulation
» Cigarettes with Reduced Tar Yield
» Agonists and Antagonists of the nAChR and its Subtypes
» Effects of Nicotine on Receptors in Different Organs
» Metabolic and Hormonal Effects of Nicotine
» Central Nervous System Effects of Nicotine
» Types of Dependence Nicotine Dependence
» Molecular Biological Aspects of Dependence
» Genetic Aspects Nicotine Dependence
» Withdrawal Symptoms Nicotine Dependence
» Immunological Reactions Caused by Cigarette Smoking
» Association Between Smoking and Lung Cancer
» Tobacco-Specific Carcinogens Genetic Factors That Increase the Risk for Bronchial Carcinoma
» The Cytochrome P450 and GST System and Carcinogenesis
» Peptide Receptors, Genetic Factors That Increase the Risk for Bronchial Carcinoma
» Exogenous Factors and Lung Cancer
» Pathophysiology of COPD Cigarette Smoking and COPD
» Genetic Factors Important Risk Factors for COPD
» Occupational and Environmental Factors
» Caveats Concerning the Informative Value of Studies
» Cigarette Smoking and Bronchial Asthma in Adults
» Bronchial Asthma in Children
» Other Lung Diseases Influenced by Cigarette Smoking
» Coronary Artery Disease and Myocardial Infarction
» Changes in Endothelial Function and Microcirculation
» Microcirculation and O Systemic Vascular Changes
» Arteriosclerotic and Inflammatory Vascular Reactions
» Genetic Factors Blood Coagulation and Fibrinolysis
» Nicotine and Ischaemic Heart Disease
» Cognitive Impairment Central Nervous System
» Influence on Cognitive Performance
» Intellectual Impairment in Childhood
» Smoker Personality Profiles and Genetic Inheritance of Smoking
» Peculiarities of the Smoker’s Personality
» Reasons for Increased Cigarette Consumption
» Comorbidity Between Depression and Smoking
» Extent of Cigarette Consumption
» Effects of Smoking in Forms of Dementia
» Smoking and Parkinson’s Disease
» Diabetic Retinopathy Ocular Diseases
» Graves’ Ophthalmopathy Ocular Diseases
» Macular Degeneration Ocular Diseases
» Ocular Tumours Ocular Diseases
» Retinal Detachment Ocular Diseases
» Lipid and Cholesterol Metabolism
» Insulin Resistance Diabetic Nephropathy
» Oesophageal Cancer Gastrointestinal Tract
» Gastrointestinal Ulcers Gastrointestinal Tract
» Cancers of the Gastrointestinal Tract
» Pancreatic Cancer Gastrointestinal Tract
» Toxic Substances and Inducers
» Kidney Cancer Urinary Tract Diseases
» Bladder Cancer Urinary Tract Diseases
» Prostatic Hyperplasia and Prostatic Cancer
» Fertility Disorders Urinary Tract Diseases
» Vitamin D and Oestrogen Metabolism
» Osteoporosis Disorders of Mineral Metabolism and Bone
» Hip Fractures Disorders of Mineral Metabolism and Bone
» Skin Changes Skin and Mucosa
» Skin Tumours Skin and Mucosa
» Breast Cancer Skin and Mucosa
» Effects of Smoking on the Placenta
» Malformations Possibly Caused by Smoking
» Smoking and Sudden Infant Death Syndrome SIDS
» Effects of Nicotine on the Foetus
» Medical Care Costs Attributable to Smoking During Pregnancy
» ETS in the Workplace and at Home
» Fibrinogen Cholesterol Endothelium and Platelets
» Markers of Inflammation Changes at the Molecular and Cellular Level
» Passive Smoking During and After Pregnancy
» Coronary Heart Disease Cardiovascular Disease
» Stroke and Subarachnoid Haemorrhage
» Respiratory Tract in Children and Teenagers
» Bronchial Carcinoma Respiratory Tract
» Indications and Diagnostic Considerations
» Self-Help Interventions by the Smoker
» Physician Advice for Smoking Cessation
» Group Behaviour Therapy Programmes
» Mass Media Communication Strategies
» E-Learning, Email and Internet for Smoking Cessation
» Evaluation of Nicotine Products
» Nicotine Chewing Gum Nicotine
» Nicotine Sublingual Tablet Nicotine Nasal Spray
» Treatment and Dosage Nicotine
» Nicotine Chewing Gum Adverse Events Associated with NRT
» Nicotine Patch Adverse Events Associated with NRT
» Nicotine Nasal Spray Adverse Events Associated with NRT
» Nicotine Inhaler Adverse Events Associated with NRT
» Nicotine Sublingual Tablet Adverse Events Associated with NRT
» Nicotine Lozenge Adverse Events Associated with NRT
» Drug Interactions During Smoking Cessation
» Contraindications for the Use of Nicotine Products
» Nicotine Formulations as OTC Products
» Contraindications and Drug Interactions
» Tranquillisers and Buspirone Other Pharmacotherapies
» Various Antidepressants Other Pharmacotherapies
» Opioid Antagonists Other Pharmacotherapies
» Silver Acetate Other Pharmacotherapies
» Therapeutic Monitoring in Smoking Cessation
» Ischaemic Heart Disease Special Therapeutic Situations
» Pregnancy Special Therapeutic Situations
» Weight Gain Special Therapeutic Situations
» Alcohol Consumption Special Therapeutic Situations
» Organic Depression Organic Depression and Schizophrenia
» Schizophrenic Patients Organic Depression and Schizophrenia
» Interactions Between Cigarette Smoking and Administration of Psychopharmaceuticals
» Pre-operative Smoking Cessation Special Therapeutic Situations
» Social Influence Inoculation Strategy
» Life Skills Strategy Prevention Programmes for Schools
» Class 2000 Health Promotion Programme
» Trier University Health Programme Long-Term Studies
» Role of Teachers in Primary Prevention
» Prevention by Restricting Sales of Tobacco Products to Minors
» Role of the Mass Media in Sales of Tobacco Products to Adolescents
» Role of Government and Community in Primary Prevention
» Effect of Tobacco Industry Advertising Messages
» Tobacco Advertising and Adolescent Smoking Initiation
» Advertising with “Light” Cigarettes
» Smoking Bans in Public Buildings and Public Spaces
» Tobacco Industry, Governmental and Non-governmental Organisations
» Politicians and Their Attitude to Smoking
» Scientists and the Tobacco Industry
» Governmental Control of Toxic Tobacco Constituents
» Bans on Advertising in Various Countries
» Tobacco Industry: Playing Down the Risks of Smoking and Passive Smoking
» Smoking and Non-smoking: Weighing the Benefits
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