Tolerance nicotine

Perkins KA, Gerlach D, Broge M, Grobe JE, Sanders M, Fonte C, Vender J, Cherry C, Wilson A (2001e) Dissociation of nicotine tolerance from tobacco dependence, J Pharmacol Exper Ther 296 849-856... 

Naloxone precipitates nicotine withdrawal in mice Naloxone induces place aversion in nicotine-dependent rats Naloxone prevents nicotine alleviation of nic. withdrawal Mu and delta agonists reduced mec-precipitated aversion Kappa antagonist suppresses mec.-precipitated aversion P-Endorphin metabolite Gly-Glu blocks aversiveness of mec-precipitated withdrawal Mec precipitates hyperalgesia in nicotine-tolerant rats NAcc Met-enkephalin increased Striatum preproenkephalin mRNA increased... 

Butschky MF, Bailey D, Henningfleld JE, Pickworth WB (1995) Smoking without nicotine delivery decreases withdrawal in 12-hour abstinent smokers. Pharmacol Biochem Behav 50 91-96 Collins AC, Romm E, Wehner JM (1988) Nicotine tolerance an analysis of the time course of its development and loss in the rat. Psychopharmacology 96 7-14 CorrigaU WA (1999) Nicotine self-administration in animals as a dependence model. Nicotine Tob Res 1 11-20... 

Stress and anxiety affect nicotine tolerance and dependence. The stress hormone corticosteroid reduces the effects of nicotine therefore, more nicotine is required to achieve the same effect. This increases tolerance to nicotine and leads to increased dependence. Animal studies have shown that stress can directly cause relapse of nicotine self-administration after a period of abstinence. Withdrawal symptoms of nicotine include irritability, impatience, hostility, anxiety, depressed mood, restlessness, increased appetite, and weight gain.2-4... 

Tobacco addiction is complex, and involves behavioral as well as pharmacologic factors. The importance of nicotine in tobacco dependence has been demonstrated in many studies (Benowitz and Jacob 1990 Surgeon General 1988). However, the neurochemical mechanisms of nicotine tolerance and dependence are not known, and the possibility exists that a reactive metabolite may be involved. 

Interestingly, unlike simple, classic competitive models, increasing drug concentration C will not overcome the inhibitor s effect Tol because Tol will increase proportionately—defeating the gains of increased drug concentration. This model has been used to simulate nicotine tolerance (61), multiple intravenous bolus dose morphine tolerance (64), and tolerance to caffeine s pressor effects (63). 

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

Brewers and bakers dried yeasts are used as dietary supplements. They contribute some protein and trace minerals, and some B vitamins, but no vitamin C, vitamin B 2 or fat-soluble vitamins. The glucose tolerance factor (GTE) of yeast, chromium nicotinate, mediates the effect of insulin. It seems to be important for older persons who caimot synthesize GTE from inorganic dietary chromium. The ceU wall fraction of bakers yeast reduces cholesterol levels in rats fed a hypercholesteremic diet. 

Tolerance is characterized by reduced responsiveness to the initial effects of a drug after repeated exposure or reduced responsiveness to a related compound (i.e., cross-tolerance). Animal studies have not provided conclusive evidence of tolerance to the effects of the centrally active compounds in toluene or trichloroethane (Moser and Balster 1981 Moser et al. 1985). Observations in humans, on the other hand, have documented pronounced tolerance among subjects who chronically inhale substances with high concentrations of toluene (Glaser and Massengale 1962 Press and Done 1967) and butane (Evans and Raistrick 1987). Kono et al. (2001) showed that tolerance to the reinforcing effects of solvents is comparable to that conditioned by nicotine but less intense than that reported with alcohol or methamphetamine use. 

In general, for smokers with cardiac disease, the benefits of nicotine replacement therapy outweigh the potential risks. In a safety and efficacy study that included veterans with cardiac disease, smoking concurrently with the nicotine patch was not associated with an increase in adverse events (Joseph et al. 1996). Although bupropion SR is generally well tolerated by smokers, it has not been adequately studied in persons with cardiac disease, and definitive conclusions regarding its safety in this patient population cannot currently be made (Society for Research on Nicotine and Tobacco 2003). 

URBERG M, ZEMEL M B (1987) Evidence for synergism between chromium and nicotinic acid in the control of glucose tolerance in elderly humans. Metabolism, 36 896-9. 

Tapper, A.R., McKinney, S.L., Nashmi, R. et al. Nicotine activation of alpha4 receptors sufficient for reward, tolerance, and sensitization. Science. 306 1029, 2004. 

Marks MJ et al. Genotype influences the development of tolerance to nicotine in the mouse. J Pharmacol Exp Ther 1991 259(1)392-402. 

Picciotto MR et al. Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature 1998 391(6663) 173—177. Popova NK et al. Altered behavior and alcohol tolerance in transgenic mice lacking MAO A a comparison with effects of... 

Netting et al. 1998). Tolerance develops to lobeline s behavioral or analgesic effects by 10 days of daily treatment, and cross-tolerance develops between lobeline and nicotine (Damaj et al. 1997). Mechanisms of Action... 

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