Withdrawal Symptoms Nicotine Dependence

There฀are฀considerable฀variations฀in฀the฀degree฀to฀which฀individuals฀experience฀these฀with- drawal฀symptoms,฀which฀may฀last฀for฀several฀weeks฀to฀months.฀Like฀alcoholics,฀many฀ ex-smokers฀are฀severely฀at฀risk฀because฀the฀least฀cause฀going฀to฀a฀restaurant฀and฀having฀ an฀alcoholic฀drink,฀meeting฀up฀with฀smokers฀may฀trigger฀a฀return฀to฀smoking.฀With฀many฀ smokers,฀however,฀it฀is฀“merely”฀the฀absence฀of฀the฀manual฀cues฀associated฀with฀the฀activ- ity฀of฀smoking฀ [120] ,฀which฀leads฀to฀a฀resumption฀of฀the฀habit฀and฀thus,฀undoes฀the฀initial฀ success฀of฀smoking฀cessation฀therapy.

4.6 Concluding Remarks

• ฀ Nicotine฀is฀one฀of฀the฀most฀potent฀toxic฀alkaloids฀with฀a฀dependence-inducing฀effect,฀ comparable฀ to฀ that฀ of฀ cocaine฀ and฀ heroin.฀ Continued฀ administration฀ in฀ the฀ form฀ of฀ tobacco฀smoking฀especially฀of฀cigarettes฀may฀lead฀to฀dependence. • ฀ Nicotine฀unfolds฀its฀effects฀by฀releasing฀CNS฀messenger฀substances,฀among฀which฀dop- amine,฀NA฀and฀5-HT฀are฀particularly฀important. • ฀ Nicotine฀acts฀by฀stimulating฀nicotinic฀acetylcholine฀receptors฀nAChRs:฀these฀are฀ion฀ transporters฀that฀occur฀in฀the฀peripheral฀and฀CNS฀and฀are฀linked฀with฀various฀transmit- ter฀systems.฀The฀structure฀of฀nAChRs฀has฀been฀largely฀elucidated฀and฀the฀various฀sub- units฀a4b2,฀a3b4,฀a7฀etc.฀can฀be฀assigned฀to฀different฀neural฀structures.฀The฀sites฀of฀ action฀of฀agonists฀and฀competitive฀and฀non-competitive฀antagonists฀can฀be฀located฀in฀ the฀receptor฀system. • ฀ Unlike฀the฀absorption฀of฀nicotine฀from฀cigarettes,฀the฀nicotine฀available฀from฀pharma- ceutical฀formulations฀is฀released฀very฀much฀more฀slowly฀and฀in฀smaller฀doses,฀and฀this฀ is฀ultimately฀the฀reason฀for฀the฀products’฀lack฀of฀any฀dependence-inducing฀effect. • ฀ In฀addition฀to฀external฀inluences,฀the฀development฀of฀nicotine฀dependence฀can฀also฀be฀ related฀to฀genetic฀factors.฀In฀this฀context,฀the฀cytochrome฀P450฀subenzyme฀2A6,฀the฀ distribution฀of฀dopamine฀receptors฀DRD1฀vs.฀DRD2฀and฀their฀alleles฀A1฀vs.฀A2,฀as฀ well฀as฀the฀DAT฀gene฀SLC6A3฀inluence฀smoking฀initiation฀and฀nicotine฀dependence. • ฀ The฀nAChR฀macromolecule฀is฀affected฀by฀several฀pathological฀conditions฀congenital฀ myasthenic฀ syndromes,฀ Alzheimer’s฀ and฀ Parkinson’s฀ disease,฀ schizophrenia,฀ some฀ forms฀of฀epilepsies,฀Gilles฀de฀la฀Tourette฀syndrome.฀A฀variety฀of฀strategies฀e.g.,฀syn- thesis฀of฀nAChR฀agonists฀and฀antagonists,฀subtle฀alterations฀to฀nAChR฀function฀or฀par- tial฀occlusion฀of฀the฀nAChR฀channel฀by฀blocking฀drugs฀will฀result฀in฀new฀therapeutic฀ modalities฀in฀the฀near฀future. 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