Effect of cigarette smoking on theophylline pharmacokinetics in rats.

The effect of acute cigarette smoke inhalation on the plasma levels of theophylline administered orally and parenterally to rats has been studied. The animals were exposed to smoke containing low- or high-nicotine/tar concentration for 10 min immediately after oral, intraperitoneal (i.p.) or intravenous (i.v.) administration of theophylline. The plasma levels of theophylline when administered orally (20 mg kg-1) were lower in the two cigarette smoke-inhaling groups than in the non-smoking restrained control group, with the lowest values in the high-nicotine/tar group. The plasma levels (8 and 12 h after administration) in the high-nicotine/tar group when theophylline was administered i.p. (10 mg kg-1), were also slightly lower than in the non-smoking restrained control group but this was not significant. When theophylline was administered i.v. (5 mg kg-1), there was no difference between the high-nicotine/tar group and the non-smoking restrained control group. These data indicate that cigarette smoke inhalation causes suppression or delay of theophylline absorption from the gastrointestinal tract.     

Influences of exposure to cigarette smoke on concentration of nicorandil in plasma of rats.

Influences of acute exposure to cigarette smoke on plasma concentrations of nicorandil administered orally and parenterally were investigated in rats by HPLC. The animals were exposed to tobacco smoke of two kinds of cigarettes using a smoking machine (i.e., the cigarette smoke contained either low or high nicotine and tar). The plasma concentration of nicorandil administered orally at a dose of 10 mg/kg had a lower absorption phase in two cigarette smoke-exposed groups, particularly in the high nicotine and tar-containing cigarette smoke-exposed group, compared with the nonsmoking control group. The AUC and MRT values in a high nicotine and tar-containing cigarette smoke-exposed group were lower and higher, respectively, than in the nonsmoking control group. However, there was no marked difference in nicorandil plasma concentrations between the cigarette smoke-exposed group and the nonsmoking control group when nicorandil was administered ip or iv at a dose of 5 mg/kg. These results suggest that cigarette smoke exposure causes the suppression or delay of absorption of nicorandil from the gastrointestinal tract.     

Effects of standard cigarette smoke and nicotine-reduced cigarette smoke on plasma concentrations of indomethacin administered orally to rats.

The influence of acute exposures to standard (ST) and nicotine-reduced (NR) cigarette smokes on the plasma concentration of orally administered indomethacin (IM, 5 mg/kg) was investigated in rats. IM plasma concentrations in the ST- and NR-groups were lower than those in the non-smoking control group, while the lowered effect in the NR-group was slightly weaker than in the ST-group. These results suggest that the plasma concentrations of IM administered orally are lowered by the acute exposure of cigarette smoke, and this influence may be attributed largely to constituents other than nicotine in the cigarette smoke as well as slightly attributable to nicotine.     

Effects of standard cigarette and nicotine-less cigarette smoke inhalings on nicorandil plasma levels in rats

The influence of cigarette smoke on nicorandil plasma levels at a dose of 10 mg/kg administered orally was investigated in rats. The animals were exposed to standard and nicotine-less cigarette smoke for 8 min using a 'smoking machine'. In nonsmoking control rats, nicorandil plasma levels increased rapidly and reached the maximum (approx. 7.6 micrograms/ml) after 1 h and then decreased gradually. On the other hand, nicorandil plasma levels in the rats inhaling standard cigarette and nicotine-less cigarette smoke reached the maximum (approx. 4.7 and 4.9 micrograms/ml, respectively) after 1-2 h. These results suggest that nicorandil plasma levels after oral administration are influenced not only by standard cigarette smoke but also by nicotine-less cigarette smoke.     

Effect of cigarette smoke on pharmacokinetics of oral,intrarectal, or intravenous indomethacin in rats

Summary The effect of cigarette smoke exposure on the pharmacokinetics of indomethacin administered orally, intravenously or intrarectally was investigated in rats. When cirgarette smoke exposure was performed for 10 min using a Hamburg II smoking machine immediately after the oral administration of indomethacin (5 mg/kg), the plasma indomethacin concentration was significantly lowered during the first 2 h after administration. However, there was no significant difference in plasma indomethacin concentration between the cigarette smoke-exposed and nonexposed control rats thereafter. Cigarette smoke exposure caused a significant decrease in the area under the concentration-time curve from 0 to 4 h (AUC_0–4) and a prolongation of the time to reach the maximum concentration (t_max). The plasma level of O-desmethyl-indomethacin (a major metabolite) was not significantly changed by cigarette smoke. When indomethacin (5 mg/kg) was administered to rats intravenously or intrarectally, cigarette smoke exposure did not have any influence on the pharmacokinetics of indomethacin or 0-desmethyl-indomethacin. The pharmacokinetic effect of cigarette smoke on orally administered indomethacin was mimicked by the subcutaneous injection of nicotine at 0.3 mg/kg but not at 0.1 mg/kg. These results suggest that acute exposure to cigarette smoke decreases the plasma concentration of indomethacin when it is administered orally but not intrarectally or intravenously. Send offprint requests to R. Oishi at the above address     

Effects of exposure to standard- and nicotine-reduced-cigarette smoke on pharmacokinetics of theophylline and cimetidine in rats.

Influences of exposure to standard- (containing nicotine and tar) and nicotine-reduced-cigarette smoke on the pharmacokinetics of theophylline (20 mg/kg, per os) and cimetidine (50 mg/kg, per os) were investigated in rats. Animals were exposed to standard- or nicotine-reduced-cigarette smoke for 8 min with a "smoking machine". In control rats, theophylline concentrations in plasma increased rapidly, peaked 2 h later, and then decreased gradually. Concentrations of theophylline in plasma of rats exposed to standard- and nicotine-reduced-cigarette smoke were suppressed in comparison with that of control rats, and the suppressive effect of nicotine-reduced-cigarette smoke was weaker than that of standard-cigarette smoke. The suppression of theophylline concentrations in plasma induced by exposure to cigarette smoke may be due to nicotine and other constituents of the cigarette smoke, even if the effects are slight. For cimetidine, no difference was found between drug concentration in plasma of rats exposed to nicotine-reduced-cigarette smoke and that of control rats; however, the drug concentration in plasma of rats exposed to standard-cigarette smoke was markedly suppressed. These results suggest that the suppression of cimetidine concentrations in plasma may be due solely to nicotine in cigarette smoke.     

The effect of inhaling thinner and/or cigarette smoke on rat kidneys

Although the effects of cigarette smoking and/or thinner inhalation on various organs have been investigated, there isn't enough study available in literature about their effects on kidneys. Therefore, in this study we investigated the effect of smoking and/or inhalation on the rat kidney. In this study, stand-alone inhalation of thinner and cigarette smoke and their application together were used to determine histopathologic changes, primarily the influences on rat kidneys. The study included 60 Wistar Albino species male rats. The 60 rats were divided into 4 groups of 15 rats each. Of the groups, three were working groups and the fourth was the control group. The rats in the first study group inhaled thinner only (T), those in the second group cigarette smoke only (CS), and the rats in the third group were made to inhale both thinner and cigarette smoke (TC). Each study group was divided into 3 subgroups each comprising 5 rats and inhalation was continued for periods of 2 wk, 4 wk, and 6 wk. Thinner was vaporized into the cage with a millipore pump at a constant pressure twice per day for 1 h for 5 days (toluene 2800-3000 ppm, acetone 500-600 ppm, isobutyl acetate 7000-8000 ppm, and isobutanol 6000-7000 ppm). Cigarette smoke was given 4 times per day for 15 min each, using a mechanism prepared with an aquarium motor (containing 1.2 mg nicotine,13 mg tar, and 13 mg carbonmonoxide; 60 puffs/min). After that, rat kidneys were removed. The kidneys were weighed and were given macroscopic and microscopic examination. There were significant differences for the thinner and thinner + cigarette smoke groups in comparison to the control group, observed in both proximal and distal tubules. However, changes in the cigarette smoke group were only in proximal tubules and were smaller in extent. Thinner has been widely used as a industrial substance. Thinner usage is an important health problem. Those sniffing thinner generally also use cigarettes. The findings of the present study reemphasize the importance of taking immediate measures in order to prevent thinner inhaling among homeless children, who pose an important social problem, and to protect people who work in industrial branches that widely use thinner.     

Post-puff respiration measures on smokers of different tar yield cigarettes

The purpose of this study was to determine the effect of different tar yield cigarette brands on the post-puff inhalation/exhalation depth and duration for established smokers of the brands. The study was conducted with 74 established smokers of 1-17 mg Federal Trade Commission (FTC) tar products. The subjects were participating in a five-day inpatient clinical biomarker study during which time they were allowed to smoke their own brand of cigarette whenever they wished. On two separate days, the subjects’ breathing pattern was measured using respiratory inductive plethysmography while they smoked one cigarette. This enabled the measurement of the post-puff inhalation volume, exhalation volume, inhalation duration, and exhalation duration for each subject after each puff on two of their own brand of cigarettes.

The subjects were grouped according to the FTC tar yield of their product: 1–3 mg; 4–6 mg; 7–13 mg; 14 + mg. The post-puff inhalation volume for the 4–6 mg group was significantly lower than both the 7–13 mg and 14+ mg groups, and the 4–6 mg group exhalation volume was significantly lower than the 14+ mg group (p < 0.05). No other differences were found at the 95% confidence level. When volumes were normalized to resting tidal volume (tidal ratio), there were no differences between the groups for any of the respiratory measures. No significant slope was found for correlations with FTC tar yield for inhalation volume (p = 0.11, mean = 833 mL, R = 0.19), inhalation tidal ratio (p = 0.93, mean = 1.73, R = ?0.01) or lung exposure time (p = 0.92, mean = 4.1?s, R = ?0.01).     

Acute effects of smoking of cigarettes with different tar content on plasma oxidant/antioxidant status

In this study, acute effects of two different types of cigarette smoking on plasma oxidant/antioxidant status were investigated. For this purpose, malondialdehyde (MDA) levels and antioxidant potential (AOP) values were measured in the plasma samples before and after cigarette smoking at fasting. After the first blood sample was obtained, second and third samples were withdrawn at 1.5 h and 3 h. In the first group, subjects smoked five cigarettes with full flavor (FF), and in the second group, five cigarettes with full-flavor low tar (FFLT). Quality classification is made mainly on the basis of tar content of the products. The cigarette with 23 mg tar is defined as FF and that with 12 mg tar as FFLT. MDA level was found to be significantly increased in the 1.5-h plasma samples of both groups, but the increase was greater in the FF group. AOP values, however, were found to be lower in the 3-h plasma samples of both groups, but the decrease was greater in the FF group compared with the FFLT group. It appears that acute smoking causes oxidant stress in blood plasma once exposed to smoke, and then this effect (MDA) begins to decrease. On the other hand, AOP is lowered due to oxidant stress created by smoke. With regard to the types of cigarettes, the FF product seems to be more oxidant than the FFLT product. Our results suggest that antioxidant supplementation might be beneficial for the smokers to cope with the oxidant load derived from cigarette smoke. It is also clearly seen from these results that cigarette manufacturers should reduce tar/nicotine ratio in their products in order to lessen the toxic effects of smoking without causing increased need to smoke.     

ACUTE EFFECTS OF SMOKING OF CIGARETTES WITH DIFFERENT TAR CONTENT ON PLASMAOXIDANT/ANTIOXIDANT STATUS

In this study, acute effects of two different types of cigarette smoking on plasma oxidant/antioxidant status were investigated. For this purpose, malondialdehyde (MDA) levels and antioxidant potential (AOP) values were measured in the plasma samples before and after cigarette smoking at fasting. After the first blood sample was obtained, second and third samples were withdrawn at 1.5 h and 3 h. In the first group, subjects smoked five cigarettes with full flavor (FF), and in the second group, five cigarettes with full-flavor low tar (FFLT). Quality classification is made mainly on the basis of tar content of the products. The cigarette with 23 mg tar is defined as FF and that with 12 mg tar as FFLT. MDA level was found to be significantly increased in the 1.5-h plasma samples of both groups, but the increase was greater in the FF group. AOP values, however, were found to be lower in the 3-h plasma samples of both groups, but the decrease was greater in the FF group compared with the FFLT group. It appears that acute smoking causes oxidant stress in blood plasma once exposed to smoke, and then this effect (MDA) begins to decrease. On the other hand, AOP is lowered due to oxidant stress created by smoke. With regard to the types of cigarettes, the FF product seems to be more oxidant than the FFLT product. Our results suggest that antioxidant supplementation might be beneficial for the smokers to cope with the oxidant load derived from cigarette smoke. It is also clearly seen from these results that cigarette manufacturers should reduce tar/nicotine ratio in their products in order to lessen the toxic effects of smoking without causing increased need to smoke.     

The induction of rat lung aryl hydrocarbon hydroxylase by diluted smoke from commercial cigarettes

Induction of pulmonary aryl hydrocarbon hydroxylase (AHH) by cigarette smoke in small rodents is well established. However, studies on dose-response relationships particularly at the lower ends of such relationships are few indeed. Availability of the British-American Tobacco Co. (B.-A.T.)-Mason inhalation system, in which precisely-calibrated dilutions of cigarette smoke can be released into an inhalation chamber, enables excellent dose-response relationships to be established. Using this inhalation system and cigarettes delivering tar (total particulate matter, water and nicotine free) equal to 1, 4 and 20 mg/cigarette, it has been shown that induction of AHH in male Sprague-Dawley rat lung is an extremely sensitive system to inhaled cigarette smoke. AHH induction was observed at a 200-s exposure to 40 puffs of a 1 : 5 dilution of smoke from an ultra mild cigarette delivering 1 mg tar. At this low concentration, it is not even possible to accurately weigh the TPM from diluted smoke in the exposure chamber. This extremely sensitive rat pulmonary enzyme system may prove valuable in the biological testing of modern low tar cigarettes.     

Influence of standard and nicotine-reduced cigarette smoke on plasma concentrations of isosorbide dinitrate and its metabolites in rats.

Rats dosed orally with isosorbide dinitrate (1 mg kg-1) were exposed to smoke from standard and nicotine-reduced cigarettes for 8 min using a smoking machine. Plasma concentrations of isosorbide dinitrate and 5-isosorbide mononitrate, one of its major metabolites were approximately equal in the exposed groups, but were lower than in the non-smoking control group. The 2-isosorbide mononitrate concentration was also lower in the group exposed to smoke from standard cigarettes. Since the pharmacokinetics were influenced by smoke from both types of cigarette smoke, the effect may be attributed in large part to non-nicotine components of the smoke.     

Plasma nicotine levels after smoking cigarettes with high, medium, and low nicotine yields.

Plasma nicotine three minutes after smoking a cigarette was measured in 10 sedentary workers in mid-morning and five hours later on four typical working days. The average mid-morning level after they had been smoking their usual cigarettes (mean nicotine yield 1-34 ng) was 150-4 nmol/l (24-4 ng/ml) (range 95-6-236-7 nmol/l (15-5-38-4 ng/ml)). Despite great variation between smokersthe mid-morning levels of each smoker were fairly consistent over the four mornings and correlated 0-82 with their carboxyhaemoglobin levels. After continuing to smoke their usual brand or switching to a high-nicotine brand (3-2 mg) average afternoon levels of 185-6 and 180-0 nmol/6 (30-1 and 29-2 ng/ml) respectively were not significantly higher than the morning levels, but after switching to low-nicotine cigarettes (0-14 mg) the plasma nicotine dropped to an average of 52-4 nmol/l (8-5 ng/ml). The changes between morning and afternoon while smoking usual or high-nicotine cigarettes showed marked individual variation. The findings suggest that the plasma nicotine level just after a cigarette depends more on the way the cigarette is smoked than on its nicotine yield or the number which have been smoked over the preceding few hours.     

Augmentation of elastase-induced emphysema by cigarette smoke: effects of reducing tar and nicotine content

The effects of reducing the tar and nicotine concentration of cigarette smoke were examined in a rat model of smoke-augmented, porcine pancreatic elastase- (PPE-) induced, pulmonary emphysema. Sixty-eight female Long-Evans rats were divided approximately evenly into seven groups: control, PPE, PPE plus sham smoke, high-tar/nicotine cigarette smoke (2R1; 38.8 mg total particulate matter and 2.2 mg nicotine per cigarette), low-tar/nicotine cigarette smoke (1R4F; 10.8 mg total particulate matter and 0.8 mg nicotine per cigarette), PPE + 2R1, and PPE + 1R4F. Three days after intratracheal administration of PPE (400 IU/kg), animals in the smoke-treated groups were exposed to 8-10 puffs of cigarette smoke daily, 7 d/wk for 12 wk. Sham-treated animals received room air in place of cigarette smoke. At the conclusion of the exposures, pulmonary function tests were performed under general anesthesia. Cigarette-smoke exposure alone did not produce significant changes in pulmonary function. Elastase-treated groups demonstrated significant increases in total lung capacity, functional residual capacity, and dynamic and static compliance, as well as significant decreases in carbon monoxide (CO) diffusing capacity and CO diffusion coefficient. Morphometric measurements of mean linear intercept demonstrated a loss of alveolar fine structure with enlargement of distal airspaces in PPE-treated rats. Exposure to either 2R1 or 1R4F cigarette smoke significantly enhanced many of the emphysematous changes produced by PPE, but there were no significant differences between the effects of the two smokes. These data indicate that reducing the tar and nicotine concentration of cigarette smoke does not lessen its ability to augment PPE-induced pulmonary emphysema in the rat.     

The effect of ranitidine, cimetidine or famotidine on low-dose post-prandial alcohol absorption

Plasma alcohol concentration following oral ingestion of 0.3 g/kg of alcohol (ethyl alcohol), one hour after an evening meal, was measured in four groups of 12 healthy subjects. Each group had a control study and a repeat study after 7 days dosing with either placebo or an H2-receptor antagonist (300 mg ranitidine nocte, 800 mg cimetidine nocte, or 40 mg famotidine nocte). There was no significant difference between the control and post-dosing studies in the integrated 4-h plasma alcohol concentration, peak plasma alcohol concentration, or time to reach peak alcohol concentration. This study shows that post-prandial alcohol absorption after 0.3 g/kg of alcohol is not affected by ranitidine, cimetidine or famotidine.     

Disease-modifying effect of ASP3258, a novel phosphodiesterase type 4 inhibitor, on subchronic cigarette smoke exposure-induced lung injury in guinea pigs

ASP3258 is a novel, orally active, selective phosphodiesterase (PDE) 4 inhibitor which has an improved therapeutic window over second generation compounds such as roflumilast and cilomilast. Here, we investigated the effect of ASP3258 on cigarette smoke exposure-induced lung injury in guinea pigs, a well-defined model for chronic obstructive pulmonary disease (COPD). COPD-like lung injury was induced by repeated cigarette smoke exposure (10 cigarettes/day, 5 days/week, for 4 weeks). Orally administered ASP3258 (0.3, 1, and 3 mg/kg) dose-dependently suppressed pulmonary accumulation of mononuclear cells and neutrophils, and the inhibitory effect of ASP3258 (1 mg/kg) was almost the same as that of roflumilast (1 mg/kg). In contrast, a glucocorticoid prednisolone (10 mg/kg, p.o.) did not show any effect. Histological examination revealed that ASP3258 treatment significantly inhibited infiltration of neutrophils and macrophages into either or both alveolar or peribronchiolar areas, as well as hyperplastic and squamous metaplastic changes of epithelium in the bronchi. Decreasing trends in histological scores for accumulation of lymphocytes in the alveoli and alveolar wall thickening were also observed in ASP3258-treated animals. Further, ASP3258 attenuated augmentation of matrix metalloproteinase-9 activity in the bronchoalveolar lavage fluid. These findings suggest that ASP3258 has therapeutic potential for treating COPD not only through inhibition of pulmonary cellular accumulation but also by preventing lung structural alterations initiated by repeated cigarette smoke exposure. To our knowledge, this is the first paper demonstrating that PDE4 inhibitors exert significant inhibitory effects on subchronic cigarette smoke exposure-induced lung injury in guinea pigs.     

Effect of grapefruit juice on drug metabolism in rats

The effect of grapefruit juice on in vivo drug metabolism was investigated in rats. The juice (4 ml or 8 ml/kg) was given orally once daily for 2 consecutive days and its effect on theophylline metabolism, pentobarbitone sleeping time and the tremorgenic action of tremorine was studied. The effect of grapefruit juice on some of these parameters was compared with that of the known drug metabolism inhibitor cimetidine given ip. Grapefruit juice at 4 ml and 8 ml/kg produced significant increases in pentobarbitone sleeping time that reached 46 and 79%, respectively, compared with 107% produced by cimetidine (50 mg/kg, ip). The juice at 4 ml/kg also significantly increased plasma theophylline concentration when measured 15, 30, 60 and 90 min after ip theophylline administration (10 mg/kg). Thereafter, no significant differences were detected in plasma drug concentrations between juice- and saline-treated animals. Administration of tremorine (25 mg/kg, ip) to saline-treated controls produced, within 2 or 3 min, tremors, piloerection, profuse salivation, defaecation, urination and chromodacryorrhesis (red tears). The onset of appearance of these signs was delayed to about 7 min in rats pretreated 1 hr earlier with either grapefruit juice (4 ml/kg, orally) or cimetidine (50 mg/kg, ip). The severity of the above signs was markedly reduced to a similar extent in both the juice- and cimetidine-treated rats. These results suggest that grapefruit juice may act as an inhibitor of drug metabolism in rats, and that its consumption may alter the disposition of certain concomitantly administered drugs.     

Effects of the new anti-ulcer agent KB-5492 on experimental gastric mucosal lesions and gastric mucosal defensive factors, as compared to those of teprenone and cimetidine.

Effects of KB-5492, a new anti-ulcer agent, on various experimental gastric mucosal lesions and mucosal defensive factors in rats were compared with those of teprenone and cimetidine. KB-5492 administered orally at 12.5-200 mg/kg inhibited water-immersion stress- and indomethacin-induced gastric mucosal lesions in a dose-dependent manner with ED50 values of 46 and 27 mg/kg, respectively, indicating that KB-5492 was more potent than teprenone but less potent than cimetidine. KB-5492, administered orally at 12.5-100 mg/kg, also inhibited ethanol-induced gastric mucosal lesions in a dose-dependent manner with an ED50 of 23 mg/kg, so KB-5492 was 3 times more potent than teprenone, whereas cimetidine produced no obvious inhibition. In addition, KB-5492, administered orally at 25 and 50 mg/kg twice daily for 10 consecutive days, significantly accelerated the healing of acetic acid-induced gastric ulcers more potently than teprenone and cimetidine. KB-5492 at anti-ulcer doses significantly increased gastric mucosal blood flow in normal anesthetized rats and inhibited the reduction of gastric mucosal hexosamine content induced by aspirin, but did not affect gastric acid secretion in pylorus-ligated rats. These results indicate that KB-5492 has potent and broad anti-ulcer properties, which are probably exerted by its enhancement of gastric mucosal defensive factors through increasing gastric mucosal blood flow and/or retaining gastric mucus, and not by its inhibition of gastric acid secretion.     

Analytical cigarette yields as predictors of smoke bioavailability

The smoke intake of 865 undisturbed smokers of over 10 cigarettes per day was measured using plasma nicotine and cotinine, and expired carbon monoxide (CO) as markers. While nicotine yields, according to Federal Trade Commission (FTC) analytical standards, varied 16-fold from 0.1 to 1.6 mg/cigarette, the corresponding plasma nicotine values varied from around 25 to 45 ng/ml, and estimated mean nicotine intake of smokers varied from around 0.75 to 1.25 mg/cigarette. Expired CO and plasma cotinine values also varied in similar proportion, but mean daily cigarette consumption was independent of the FTC nicotine yield of the cigarettes smoked. The results indicate that pharmacodynamic satiation causes behavioral regulation, and that smokers of very high yield brands compensate downward, and vice versa. The ratio of tar yield to nicotine yield usually increases with increasing tar yield; therefore tar intake is likely to increase at higher tar yields, even though the increment of nicotine intake is small. It follows that FTC analytical determinations are poor predictors of relative intake of nicotine, CO, or tar, while rankings based on mean tar-to-nicotine ratio of a brand's smoke could be more meaningful. Moreover, the considerable variation of individual smoking behavior suggests that precise numerical rankings of cigarettes are not justified. An analogic ranking of cigarettes into a few broad classes would better reflect the realities and expectations of average consumers.     

Sensory blockade of smoking satisfaction

Cigarette smokers were presented with controlled doses of cigarette smoke to determine whether the resulting reduction in cigarette craving depended upon perceiving the sensory qualities of the smoke. Cigarette craving was assessed before and after inhaling controlled doses of smoke in two conditions: (1) Local anesthesia of the upper and lower respiratory airways, induced by mouth rinsing, gargling and inhalation of a mist containing the topical anesthetic lidocaine; and (2) no-anesthesia control, in which all solutions were saline. A sham smoking procedure was presented in both conditions. Craving and ad lib smoking behavior were also assessed 30 minutes after controlled smoking. The results indicated that smoke, as opposed to sham puffs, significantly reduced reports of cigarette craving, and local anesthesia significantly blocked this immediate reduction in craving produced by smoke inhalation. Puffs were also rated as less desirable in the anesthesia condition. Thirty minutes after smoking, craving was no different in the anesthesia and saline control conditions. However, craving as well as smoking intake in both conditions was less when smoke had been given previously than in the sham smoking control. These results suggest that sensory cues accompanying inhalation of cigarette smoke are important determinants of immediate smoking satisfaction. However, the sustained effects of smoke intake on subsequent smoking behavior (30 min later) may be mediated by processes other than sensory stimulation of the respiratory tract, such as plasma nicotine levels.