CORK Bibliography: Nicotine, Therapeutic Use

28 citations. January 2003 to present

Prepared: March 2009

Benowitz NL. Basic cardiovascular research and its implications for the medicinal use of nicotine. (editorial). Journal of the American College of Cardiology 41(3): 497-498, 2003. (18 refs.)

Benowitz NL. Nicotine and postoperative management of pain. (editorial). Anesthesia and Analgesia 17(3): 739-741, 2008. (19 refs.)

Berman ML. Current issues in tobacco regulation, litigation, and policy. Symposium: Tobacco Litigation without the smoke? Cigarette companies in the smokeless tobacco industry. Journal of Health Care Law & Policy 11: 7-56, 2008. (27 refs.)

SUMMARY: ... The MSA broadly prohibits directly or indirectly targeting underage youth in the "advertising, promotion or marketing of Tobacco Products" (and, as discussed above, the definition of "Tobacco Products" includes smokeless tobacco). ... In the case of smokeless tobacco, narrowly-focused litigation may serve to educate the public about the harms of smokeless tobacco and the fact that the tobacco industry has made - and continues to make - deliberate choices that increase the toxicity of smokeless tobacco products. ... Reynolds and Philip Morris have not made any explicit harm reduction claims on behalf of their smokeless tobacco products, USST has argued to the U.S. ... Department of Health and Human Services that "any comprehensive evidence-based tobacco control program should include a tobacco harm reduction strategy providing that cigarette smokers who do not quit and do not use medical nicotine products should be encouraged to switch completely to smokeless tobacco ... ." Of course, tobacco companies will continue to argue in court, as they have in the past, that smoking is an "adult choice" (despite the fact that most smokers became addicted to cigarettes as minors) and that the public is well-informed of the health risks of smoking (despite the companies' decades-long conspiracy to mislead the public about the dangers of smoking).

Cox LS; Patten CA; Krahn LE; Hurt RD; Croghan IT; Wolter TD et al. The effect of nicotine patch therapy on depression in nonsmokers: A preliminary study. Journal of Addictive Diseases 22(4): 75-85, 2003. (27 refs.)

Prior uncontrolled studies of nonsmokers with major depressive disorder (MDD) indicate rapid reduction in depressive symptoms with nicotine patch therapy. This randomized, double-blind, placebo-controlled pilot study examined the effect of nicotine patch. therapy on depressive symptoms in non-medicated nonsmokers with current MDD. Due to recruitment difficulties, only 7 were enrolled and of these 6 (5 females, I male) completed the study. Participants received either placebo (n = 4) or active (n = 2) patch therapy for 8 days. They completed daily clinic visits during patch therapy and a final visit on Day 12. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HRSD). The mean change in HRSD scores of all participants decreased (p = 0.021) from baseline by Day I of patch use. Similar decreases in HRSD scores were observed for placebo and active patch groups. Among the placebo participants, the mean HRSD score decreased (p = 0.038) by Day 2. The study needs replication with a larger sample and utilizing novel recruitment strategies.

Habib AS; White WD; El Gasim MA; Saleh G; Polascik TJ; Moul JW et al. Transdermal nicotine for analgesia after radical retropubic prostatectomy. Anesthesia and Analgesia 107(3): 999-1004, 2008. (32 refs.)

BACKGROUND: Previous animal and human studies suggested that nicotine might have an antinociceptive effect. We hypothesized that the preoperative application of a 7 mg nicotine patch would result in reduced postoperative analgesic requirements in patients undergoing radical retropubic prostatectomy (RRP) under general anesthesia. METHODS: Nonsmokers undergoing RRP under general anesthesia were enrolled in this prospective, double-blind, placebo-controlled Study. Patients were randomly assigned to receive a patch of 7 mg nicotine or placebo applied behind the ear 30-60 min before induction of anesthesia. The anesthetic technique was standardized. Postoperative analgesia was provided with a standardized morphine patient-controlled analgesia and 6 hourly ketorolac 15 mg IV. Data were collected in the postanesthesia care unit and at 6, 12, and 24 h after Surgery. RESULTS: Ninety patients were included in the analysis: 44 in the nicotine group and 46 in the placebo group. The groups did not differ significantly with respect to age, height, weight, ASA class, length of surgery, or amounts of intraoperative fentanyl received. The nicotine group showed significantly lower cumulative morphine consumption at 24 h (mean +/- SD): 33.3 +/- 30.8 mg vs 44.7 +/- 26.4 mg (P = 0.0059, time X treatment P = 0.0031). However, the repeated measures tests found no difference in amount of pain reported on coughing or at rest, either as treatment effects or in interaction with time. In post hoc comparisons, there was no significant difference in amount of pain reported on coughing or at rest at any of the times assessed. There were also no significant differences between the groups ill the incidence of postoperative nausea and vomiting or the need for rescue antiemetics. However, the maximum nausea verbal rating scale score was higher in the nicotine than in the placebo group (median, 25th to 75th percentiles = 4, 0-6 vs 0, 0-6, P 0.0158). There was a significant negative correlation between the 24 h plasma nicotine levels and postoperative morphine consumption in the postanesthesia care unit (P = 0.049), as well as at 6, 12, and 24 h (P = 0.002). CONCLUSION: The preoperative application of a 7 mg nicotine patch resulted in a significant reduction in opioid consumption in patients undergoing RRP under general anesthesia. Despite this reduction in opioid use, there was no reduction in pain scores or postoperative nausea and vomiting with the use of transdermal nicotine.

Hellstrom-Lindahl E; Mousavi M; Ravid R; Nordberg A. Reduced levels of A beta 40 and A beta 42 in brains of smoking controls and Alzheimer's patients. Neurobiology of Disease 15(2): 351-360, 2004. (75 refs.)

The effects of nicotine on levels of Abeta 40 and Abeta 42 and nicotinic receptor binding sites were studied in brains from nonsmoking and smoking patients with Alzheimer's disease (AD) and aged-matched controls. The levels of soluble and insoluble Abeta 40 and Abeta 42 in frontal cortex and Abeta 40 in temporal cortex and hippocampus were significantly decreased in smoking AD patients compared to nonsmokers with AD. In smoking controls the levels of soluble and insoluble Abeta 40 and Abeta 42 in the frontal and temporal cortex were significantly lower than in nonsmoking controls. The binding of [H-3]cytisine in temporal cortex was significantly increased in smokers with AD compared to nonsmokers with AD. In smoking controls [H-3]cytisine and [H-3]epibatidine binding were significantly increased from 1.5- to 2-fold compared to nonsmoking controls whereas binding sites for [I-125]alpha-bungarotoxin was less up-regulated. These results indicate that selective nicotinic receptor agonists may be a novel protective therapy in AD by reducing Abeta levels as well as the loss of nicotinic receptors in AD brain.

Hong D; Conell-Price J; Cheng S; Flood P. Transdermal nicotine patch for postoperative pain management: A pilot dose-ranging study. Anesthesia and Analgesia 107(3): 1005-1010, 2008. (29 refs.)

BACKGROUND: Nicotine has been shown to be antinociceptive in the postoperative period in animal studies. Human Studies with nasal nicotine sprays have had mixed results, possibly due to variability in pharmacokinetics and potential patient variables such as exposure to nicotine in tobacco smokers. In this pilot study, we examined the analgesic effect of a transdermal nicotine. patch applied before surgery in nonsmokers. METHODS: We conducted a randomized, double-blind, prospective placebo-controlled trial of 40 subjects, undergoing general Surgery that required postoperative patient-controlled analgesia and an overnight hospital admission. Immediately before surgery, a transdermal nicotine patch containing 0, 5, 1.0, or 15 mg was applied. The primary outcome variable was pain report using a numerical rating scale (NRS) in the first hour after Surgery and over the next 5 days. Secondary outcomes were pain medication use, hemodynamic values, nausea, and sedation. RESULTS: Patients treated with nicotine reported lower pain scores when compared with those treated with placebo during the first hour after Surgery (P = 0.003, average NRS decrease = 1.4, 95% CI = 0.3-2.6) and for 5 days after surgery (P = 0.03, average NRS decrease 1.0, 95% CI = 0.1-1.9). There was no increased benefit of nicotine with doses larger than 5 mg. There was a trend suggesting decreased pain medicine use, increased nausea, decreased tachycardia, and slightly decreased systolic blood pressure in the nicotine groups, but these values did not reach significance. CONCLUSIONS: Transdermal nicotine, 5-15 mg, reduced postoperative pain scores but failed to decrease the need for opioid analgesics or opioid-related side effects after general Surgical procedures.

Howson AL; Batth S; Ilivitsky V; Boisjoli A; Jaworski M; Mahoney C et al. Clinical and attentional effects of acute nicotine treatment in Tourette's syndrome. European Psychiatry 19(2): 102-112, 2004. (54 refs.)

Evidence from pre-clinical infrahuman investigations, open-label clinical trials, and a single controlled trial found acute nicotine treatment potentiated up to 4 weeks neuroleptic-induced reductions of dyskinetic symptoms characterizing Tourette's syndrome (TS). Given the attentional disturbances associated with this syndrome, and the improvements in attentional processes reported with nicotine, this randomized, double-blind, placebo-controlled trial examined the acute (4 h) and sustained (2 weeks) effects of a single dose of transdermal nicotine on clinical (i.e., tics), attentional (continuous performance task, event-related potentials, patient and parental reports) and behavioral symptoms in 23 children and adolescents with TS receiving neuroleptic treatment. In the 14 evaluable patients with complete primary efficacy data, nicotine (compared to placebo) failed to alter symptoms at 4 h but counteracted ERP-P300 signs of diminished attention seen 2 weeks following placebo treatment. Secondary efficacy measures, including patient self-reports and parental ratings, found nicotine to reduce complex tics and improve behaviors related to inattention. Additional work with intermittent dosing schedules is required to characterize optimal clinical and cognitive effects with nicotine treatment.

Hughes JR. Significance of off-label use of NRT. Commentary. Addiction 103(10): 1704-1705, 2008. (13 refs.)

Ingram JR; Rhodes J; Evans BK; Thomas GAO. Preliminary observations of oral nicotine therapy for inflammatory bowel disease: An open-label phase I-II study of tolerance. Inflamatory Bowel Diseases 11(12): 1092-1096, 2005. (18 refs.)

Background: Transdermal nicotine provides benefit in active ulcerative colitis but is often associated with adverse events (AEs). An oral formulation has been developed to minimize AEs. This Study was undertaken to make initial observations on the safety and tolerance of oral nicotine therapy in inflammatory bowel disease; the effect oil disease activity was also noted. Methods: Twenty-six patients with Ulcerative colitis, 11 with active disease, and 5 patients with Crohn's colitis (2 with active disease) were given oral nicotine in 3-mg capsules, gradually increasing the dose to the maximum tolerated. AEs were recorded, concomitant prednisolone and/or azathioprine were reduced where possible, and disease activity was reassessed at the end of nicotine treatment. Results: Patients were followed for LIP to 12 months. Twenty-nine of 31 could tolerate at least 6 mg of nicotine each clay, and 5 patients tolerated at least 18 mg daily. Twenty-four patients had nicotine-related nonserious AEs; over one half Occurred during the period of dose escalation, but 7 discontinued treatment because of them. Six of the 13 patients with active disease became asymptomatic, whereas 3 patients in remission developed active symptoms; 11 patients reduced their concomitant medication. Conclusions: Oral nicotine is a safe potential treatment of inflammatory bowel disease, but there is considerable variation in tolerance.

Ingram JR; Routledge P; Rhodes J; Marshall RW; Buss DC; Evans BK et al. Nicotine enemas for treatment of ulcerative colitis: A study of the pharmacokinetics and adverse events associated with three doses of nicotine. Alimentary Pharmacology & Therapeutics 20(8): 859 -865, 2004. (16 refs.)

Background: Transdermal nicotine is of value in active ulcerative colitis but causes adverse events because of systemic absorption. Nicotine enemas may give rise to fewer adverse events. Aim: To assess the pharmacokinetics of nicotine enemas in three doses. Methods: Thirteen volunteers, all non-smokers but three ex-smokers, were given enemas on separate occasions containing 3, 6 and 9 mg of nicotine, in ascending dose order. Adverse events were recorded and blood samples taken over 8 h for measurement of serum nicotine and cotinine. Results: Enemas were retained by most subjects. Eleven of 14 adverse events were 'early'- 30-105 min after the enema, corresponding to maximum plasma nicotine concentrations; three events were later, 4-8 h after the enema and unrelated to the t(max). 'Early' adverse events occurred in eight subjects - six with 9 mg. The three highest plasma nicotine concentrations were with 9 mg and associated with headache, nausea and sweating. Only one had adverse events with 3 mg and withdrew from the study. Nicotine C-max with 6 and 9 mg doses were respectively two and three times the value with 3 mg. Peak nicotine concentrations occurred 44-50 min after the enema. Conclusion: The 6 mg dose of nicotine probably represents the dose to use in clinical practice - for the highest therapeutic dose with a low risk of adverse events.

Klaz I; Kochba I; Shohat T; Zarka S; Brenner S. Severe acne vulgaris and tobacco smoking in young men. Journal of Investigative Dermatology 126(8): 1749-1752, 2006. (24 refs.)

As the relationship between tobacco smoking and acne remains unclear, we examined the relationship between cigarette smoking and severe acne in a large cohort of young men. Trained nurses interviewed subjects upon discharge from compulsory military service, regarding family history, habits, and tobacco smoking habits. Data was correlated with severe acne status, as diagnosed and coded by board- certified dermatologists. In total, 27,083 male subjects participated in the study from 1983 to 2003, of which 237 (0.88%) had severe acne, 11,718 (43.27%) were active smokers, and 15,365 (56.73%) were nonsmokers at the time of interviews. Active smokers showed a significantly lower prevalence of severe acne (0.71%) than nonsmokers (1.01%) ( P 0.0078). An inverse dose- dependent relationship between severe acne prevalence and daily cigarette consumption became significant from 21 cigarettes a day (chi(2) and trend test: P < 0.0001), odds ratio: 0.2 (95% CI: 0.06 - 0.63). The study did not aim to establish a temporal correlation, and passive smoking and acne treatments were not measured. Previous in vitro and clinical studies strongly support an association with nicotine. We suggest a trial with topical nicotine treatment for acne to further investigate this association.

Lemay S; Blanchet P; Chouinard S; Masson H; Soland V; Bedard MA. Poor tolerability of a transdermal nicotine treatment in Parkinson's disease. (review). Clinical Neuropharmacology 26(5): 227-229, 2003. (15 refs.)

Studies assessing the effect of transdermal nicotine in Parkinson's disease (PD) have generated mixed results regarding its efficacy to treat motor and cognitive deficits. These studies generally reported good tolerability in nonsmoking PD patients. The authors report the tolerability data of an open trial with transdermal nicotine in PD. Twenty-two therapeutically well-controlled nonsmoking PD patients received a transdermal nicotine treatment over 25 days according to the following fixed titration schedule: 7 mg for the first 11 days, 14 mg for the next 11 days, and 21 mg for the last 3 days. Fourteen PD patients (64%) had side effects such as nausea, vomiting, and dizziness, and 10 of them withdrew from the study. Factors such as age, body mass index, disease duration, and motor disability were not related to this intolerance. Transdermal nicotine can produce unpleasant adverse effects in patients with PD. Given that similar doses of nicotine were better tolerated in previous studies, the authors suspect the pharmacokinetic profile of the transdermal delivery system to be a determining factor in the effect of nicotine treatment in PD.

Lemay S; Chouinard S; Blanchet P; Masson H; Soland V; Beuter A et al. Lack of efficacy of a nicotine transdermal treatment on motor and cognitive deficits in Parkinson's disease. (review). Progress in Neuro-Psychopharmacology & Biological Psychiatry 28(1): 31-39, 2004. (76 refs.)

Studies assessing the efficacy of nicotine in Parkinson's disease (PD) have generated contradictory results. The controversy seems to stem from uncontrolled factors including the lack of objective measures, the practice effect in a test-retest design, and the absence of plasmatic dosage. This study aimed at further controlling these factors using transdermal nicotine in PD. Methods: Twenty-two nonsmoking PD patients received a transdermal nicotine treatment over 25 days in increasing titrated doses. Motor and cognitive assessments were carried out on days 11 and 25 (low-dose and high-dose assessments, respectively) and after a 14-day washout period. Results: Patients tolerated nicotine poorly. Thirteen (59%) withdrew, mostly because of acute side effects. In the remaining nine patients, nicotine neither improved nor worsened motor or cognitive functioning in comparison with 10 age, gender and education matched controls. Conclusions: Transdermal nicotine is not effective in treating motor and cognitive deficits in PD. The results obtained with our objective measures confirm a recent double-blind, placebo-controlled study that used clinical measures. It is possible that nicotine lacks specificity in targeting critical nicotinic receptors that might be involved in PD pathophysiology. The low tolerability may be related to such a lack of specificity of nicotine, which would directly stimulate the autonomic nervous system.

Liu Q; Zhao BL. Nicotine attenuates beta-amyloid peptide-induced neurotoxicity, free radical and calcium accumulation in hippocampal neuronal cultures. British Journal of Pharmacology 141(4): 746-754, 2004. (68 refs.)

1 Recent studies indicate that neuronal loss in Alzheimer's disease (AD) is accompanied by the deposition of beta-amyloid protein (Abeta) in senile plaques. Nicotine as a major component of cigarette smoke has been suggested to have a protective effect for neurons against Abeta neurotoxicity.2 Our present study demonstrates that nicotine protected cultured hippocampal neurons against the Abeta-induced apoptosis. Nicotine effectively inhibits apoptosis in hippocampal cultures caused by Abeta(25-35) or Abeta(1-40) treatment and increase of caspase activity induced by Abeta(25-35) or Abeta(1-40)3 Measurements of cellular oxidation and intracellular free Ca2+ showed that nicotine suppressed Abeta-induced accumulation of free radical and increase of intracellular free Ca2+.4 Cholinergic antagonist mecamylamine inhibited nicotine-induced protection against Abeta-induced caspase-3 activation and ROS accumulation.5 The data show that the protection of nicotine is partly via nicotinic receptors. Our results suggest that nicotine may be beneficial in retarding the neurodegenerative diseases such as AD.

McClernon, FJ; Hiott, FB; Westman, EC; Rose, JE; Levin, ED. Transdermal nicotine attenuates depression symptoms in nonsmokers: A double-blind, placebo-controlled trial. Affilia 189(1): 125-133, 2006. (58 refs.)

Rationale" Despite established links between nicotine dependence and depression, little research has examined the effects of nicotine on depression symptoms. Objective: This study evaluated the acute and chronic effects of transdermal nicotine in nonsmokers with baseline depression symptoms during a 4-week, double-blind, placebo-controlled trial. Methods: Nonsmokers with scores >= 10 on the Center for Epidemiological Studies Depression scale (CES-D) were recruited from the community. Mood and cognitive performance were measured at baseline ( day 0) and at 1, 8, 21, and 28 days. Participants were randomly assigned to wear a placebo or nicotine patch for 4 weeks (3.5 mg/day during weeks 1 and 4; 7 mg/day during weeks 2 and 3). The final sample consisted of 11 nonsmokers with a mean baseline CES-D score of 27.36 (SD=10.53). Results: Salivary nicotine levels indicated the majority of participants were compliant with treatment. Acute nicotine did not alter mood. After adjusting for baseline values, chronic nicotine resulted in a significant decline in CES-D scores at day 8 (3.5 mg/day), but returned to placebo levels by the last visit. This return to baseline levels was coincident with a decrease in nicotine administration from 7 to 3.5 mg/day. A similar trend for improved response inhibition as measured by the Conners Continuous Performance Task was also observed. Reported side effects were infrequent and minimal. Conclusion: These findings suggest a role for nicotinic receptor systems in the pathophysiology of depression and that nicotinic compounds should be evaluated for treating depression symptoms.

Metz CN; Gregersen PK; Malhotra AK. Metabolism and biochemical effects of nicotine for primary care providers. (review). Medical Clinics of North America 88(6): 1399+, 2004. (109 refs.)

Nicotine is a colorless and volatile liquid alkaloid naturally occurring in the leaves and stems of Nicotiana tabacum and Nicotiana rustica. Nicotine, the primary component of tobacco, is responsible for both tobacco product addiction (with chronic exposure) and the odor associated with tobacco. In addition to cigarettes, nicotine is found in chewing gum, transdermal patches, nasal spray, and sublingual tablets. Following its inhalation and absorption, nicotine and its metabolic products exert diverse physiologic and pharmacologic effects. This article covers the absorption and metabolism of nicotine, nicotine toxicity, pharmacologic effects of nicotine, nicotine-drug interactions, and the use of nicotine for the treatment of disease.

Poltavski DV; Petros T. Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits. Physiology & Behavior 87(3): 614-624, 2006. (42 refs.)

Extant evidence suggests a possibility of self-medication to account for greater prevalence of cigarette smoking among adults with ADHD as they tend to show improvements on affective and cognitive measures, particularly on measures of sustained attention following nicotine administration. The present study was conducted to evaluate whether adult non-smokers with low attentiveness might exhibit greater improvements on measures of sustained attention than those with higher attentiveness using neuropsychological tests that had previously shown sensitivity to ADHD. On the basis of their scores on attention scales used in the diagnosis of adult ADHD, 62 male non-smokers were divided into 2 groups of either low or high attentiveness and treated with either a placebo or 7 mg nicotine patch. After 6 h of patch application each participant completed the Wisconsin Card Sorting Test (WCST), classic Stroop task, and Conners' Continuous Performance Test (CPT), which were administered in a counterbalanced order and a double-blind manner. No significant drug or group differences were observed on the Stroop task. On the Conners' CPT participants in the low attention group treated with nicotine committed significantly fewer errors of commission, showed improved stimulus detectability and fewer perseverations than those in the low attention placebo group. On the WCST nicotine significantly impaired the ability of participants in the high attention group to learn effective strategies to complete the test with fewer trials. The results showed nicotine-induced improvement on some measures of sustained attention in the low attention group and some decrement in working memory in the high attention group, which suggests that nicotine tends to optimize rather than improve performance on cognitive tasks.

Punnoose S; Belgamwar MR. Nicotine for schizophrenia. Cochrane Database of Systematic Reviews 1: article CD004838, 2006. (54 refs.)

Background: The proportion of people with schizophrenia who smoke is very high, and as a rule, they tend to be heavier smokers when compared to the general population and those with other psychiatric disorders. Nicotine, the psychoactive component in tobacco, is thought to produce psychological effects that help to alleviate psychotic symptoms. Objectives: To examine the effects of nicotine and related products in the treatment of schizophrenia. Search strategy We electronically searched the Cochrane Schizophrenia Group's Register ( April 2005), supplemented with manually inspecting references of all identified studies and by contacting authors of studies where required. Selection criteria We included all randomised clinical trials comparing nicotine or related products as a sole or adjunctive treatment for people with schizophrenia or other similar serious, non-affective psychotic illness. Data collection and analysis Citations and, where possible, abstracts were independently inspected by reviewers and the papers ordered were scrutinised and quality assessed. We extracted and evaluated data independently and analysed on an intention to treat basis. We would have calculated fixed effect relative risk (RR), number needed to treat/harm (NNT/ H) and their 95% confidence intervals (CI) for binary outcomes and for continuous non-skewed data we would have calculated weighted mean differences. We would have excluded data if loss to follow-up had been greater than 50% and inspected the data for heterogeneity. Main results: We did not find any trials that met the inclusion criteria. Authors' conclusions: There ought to be further research of nicotine for schizophrenia by parallel group design randomised controlled trials investigating the effects of nicotine on symptoms of schizophrenia as well as on side effects of antipsychotic drugs. We further note that authors and journals should conform to the CONSORT guidelines when publishing the research articles, especially when disclosing all the data available from a particular study.

Romanelli MN; Gratteri P; Guandalini L; Martini E; Bonaccini C; Gualtieri F. Central nicotinic receptors: Structure, function, ligands, and therapeutic potential. (review). ChemMedChem 2(6): 746-767, 2007. (271 refs.)

The growing interest in nicotinic receptors, because of their wide expression in neuronal and non-neuronol tissues and their involvement in several important CNS pathologies, has stimulated the synthesis of a high number of ligands able to modulate their function. These membrane proteins appear to be highly heterogeneous, and still only incomplete information is available on their structure, subunit composition, and stoichiometry. This is due to the lack of selective ligands to study the role of nAChR under physiological or pathological conditions; so for, only compounds showing selectivity between alpha 4 beta 2 and alpha 7 receptors have been obtained. The nicotinic receptor ligands have been designed starting from lead compounds from natural sources such as nicotine, cytisine, or epibatidine, and, more recently, through the high-throughput screening of chemical libraries. This review focuses on the structure of the new agonists, antagonists, and allosteric ligands of nicotinic receptors, it highlights the current knowledge on the binding site models as a molecular modeling approach to design new compounds, and it discusses the nAChR modulators which have entered clinical trials.

Willoughby JO; Pope KJ; Eaton V. Nicotine as an antiepileptic agent in ADNFLE: An n-of-one study. Epilepsia 44(9): 1238-1240, 2003. (6 refs.)

Purpose: To test nicotine patch treatment for a patient with a defined mutation for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) whose seizures were refractory to standard antiepileptic therapy. Methods: Open and double-blind trials of nicotine patches in an "n-of-one" study. The double-blind trial comprised periods during which either placebo or nicotine patches were each used for three periods of 2 weeks, randomized in a double-blind manner. Results: In an open study, nicotine patches reduced seizures from 1.65 +/- 2.36 to 0.01 +/- 0.0 seizures per day (p < 0.0001). In a double-blinded placebo-controlled phase, the average frequency of seizures on nicotine versus placebo was 0 +/- 0 versus 0.56 +/- 1.14 seizures per day (p < 0.0001).Conclusions: Nicotine patches may be of benefit to some individuals with ADNFLE.

Turan A; White PF; Koyuncu O; Karamanlioolu B; Kaya G; Apfel CC. Transdermal nicotine patch failed to improve postoperative pain management. Anesthesia and Analgesia 107(3): 1011-1017, 2008. (30 refs.)

BACKGROUND: A single 3 mg intranasal dose of nicotine has been reported to have analgesic properties. We designed placebo-controlled study to test the hypothesis that transdermal nicotine (TDN) administered over a 3-day period would decrease postoperative pain and opioid analgesic usage and improve the recovery process after lower abdominal surgery. METHODS: Ninety-seven patients undergoing abdominal hysterectomy procedures were randomly assigned to one of two treatment groups: (1) control group received inert (sham) patches 1 h before and for 2 days after surgery, or the (2) nicotine group received TDN 30 (21 mg nicotine) patches I h before induction of anesthesia and for two additional days after surgery. The anesthetic technique was identical in both groups, and the postoperative assessments included verbal rating scales for pain and sedation, IV patient-controlled analgesia morphine usage, quality of recovery assessment, recovery of bowel function, resumption of normal activities, and patient satisfaction with their pain management. Follow-up evaluations were performed at 1 and 3 mo after the operation to assess late recovery events. RESULTS: Postoperative patient-controlled analgesia morphine usage and pain scores while supine or sitting up, intraoperative fentanyl use, oral analgesic consumption, return of bowel sounds, and passage of flatus did not differ between the two groups. Although ambulation and hospitalization times, as well as, quality of recovery scores, did not differ, resumption of oral intake was delayed in the nicotine group. Discharge eligibility scores were higher in the nicotine group at 48 and 72 h compared with the control group, but the time to return to work was 19 days in both treatment groups. CONCLUSIONS: Perioperative administration of high-dose TDN patch did not improve postoperative pain control or decrease the analgesic requirement after pelvic gynecological surgery. Despite delayed resumption of oral intake, more patients in the nicotine group were ready for discharge at 48 and 72 h after surgery. However, times to resuming activities of daily living were similar in both groups.